• Aerobic exercise
• Bone metabolism
• Exercise intensity
• Mechanical stress
• Mice

• Male
• Animals
• Mice
• beta Catenin
• Mice, Inbred C57BL
• Bone and Bones
• Bone Density
• Bone Resorption

• 19H04050 Japan Society for the Promotion of Science

• balance
• meta-analysis
• stroke
• walking function
• whole-body vibration training

• Chinese traditional fitness exercise
• bone metabolism
• bone mineral density
• osteoporosis
• therapy

• Bone mineral density
• Exercise training
• Meta-analysis
• Osteoporosis
• Postmenopausal

• animal models
• bone
• bone loss
• dexamethasone
• glucocorticoid induced osteoporosis
• methylprednisolone
• therapy

• Animals
• Biomechanical Phenomena/drug effects
• Bone Resorption/pathology
• Bone and Bones/drug effects
• Bone and Bones/pathology
• Disease Models, Animal
• Female
• Glucocorticoids/adverse effects
• Male
• Mice, Inbred C57BL
• Osteoporosis/chemically induced
• Osteoporosis/pathology
• Rats, Sprague-Dawley
• Mice
• Rats

Emerging evidence suggests that the progesterone-mediated receptor activator of nuclear factor κB (RANK)/soluble RANK ligand (sRANKL)/osteoprotegerin (OPG) pathway plays an important role in mammary carcinogenesis and is hyperactivated in germline (g)BRCA1/2 mutation carriers. We analyzed the effects of a 3-month intensive lifestyle intervention within the LIBRE-1 study on the serum levels of OPG and sRANKL and hypothesized that the intervention program provides a beneficial impact on the biomarkers by increasing OPG and reducing sRANKL serum concentrations.

Serum levels of OPG and sRANKL of 49 gBRCA1/2 mutation carriers were quantified using enzyme-linked immunosorbent assays. We used previously collected blood samples from participants of the prospective LIBRE-1 study, who were randomized into an intervention group (IG), increasing physical activity and adherence to the Mediterranean diet (MedD) through supervised sessions from study entry to the first study visit after 3 months and a usual-care control group (CG). Differences in biomarker levels before and after the 3-month intervention were tested within and between study groups.

The lifestyle intervention resulted in a significant increase in OPG for participants in both the IG (q = 0.022) and CG (q = 0.002). sRANKL decreased significantly in the IG (q = 0.0464) and seemed to decrease in the CG (q = 0.5584). An increase in the intake of Omega-3 polyunsaturated fatty acids was significantly associated with an increase in OPG (r = 0.579, q = 0.045). Baseline serum levels of sRANKL were a strong predictor for the change of sRANKL in the course of the intervention (ß-estimate = − 0.70; q = 0.0018). Baseline physical fitness (assessed as VO₂peak) might predict the change of OPG in the course of the intervention program (ß-estimate = 0.133 pg/ml/ml/min/kg; p = 0.0319; q = 0.2871).

Findings from this pilot study seem to confirm our hypothesis by showing an increase in OPG and decrease in sRANKL over a 3-month lifestyle intervention and suggest that increased physical activity and adherence to the MedD are potent modulators of the biomarkers OPG and potentially sRANKL.

The online version contains supplementary material available at 10.1007/s10549-021-06400-7.

• BRCA1/2 mutation carriers
• Breast cancer
• Fatty acids
• Lifestyle intervention
• Mediterranean diet
• OPG
• Physical activity
• RANKL

• RAW264.7 cells
• THP-1 cells
• miRNA-151a-3p
• osteoclast differentiation
• postmenopausal osteoporosis

• Aged
• Aged, 80 and over
• Animals
• Cell Differentiation
• Female
• Humans
• MicroRNAs/metabolism
• Middle Aged
• Osteoclasts/metabolism
• Osteoporosis, Postmenopausal/blood
• Osteoporosis, Postmenopausal/therapy
• Rats

• no funding

• bone–muscle crosstalk
• myokines
• osteokines
• osteosarcopenia
• physical activity
• prevention strategy

The multifold benefits of regular physical exercise have been largely demonstrated in human and animal models. Several studies have reported the beneficial effects of physical activity, both in peripheral tissues and in the central nervous system (CNS). Regular exercise improves cognition, brain plasticity, neurogenesis and reduces the symptoms of neurodegenerative diseases, making timeless the principle of “mens sana in corpore sano” (i.e., a healthy mind in a healthy body). Physical exercise promotes morphological and functional changes in the brain, acting not only in neurons but also in astrocytes, which represent the most numerous glial cells in the brain. The multiple effects of exercise on astrocytes comprise the increased number of new astrocytes, the maintenance of basal levels of catecholamine, the increase in glutamate uptake, the major release of trophic factors and better astrocytic coverage of cerebral blood vessels. The purpose of this review is to highlight the effects of exercise on brain function, emphasize the role of astrocytes in the healthy CNS, and provide an update for a better understanding of the effects of physical exercise in the modulation of astrocyte function.

• astrocytes
• brain functions
• exercise
• neuron

• Adaptation, Physiological/physiology
• Animals
• Astrocytes/physiology
• Brain/physiology
• Exercise/physiology
• Humans
• Neurogenesis/physiology
• Neuronal Plasticity/physiology
• Neurons/physiology
• Physical Conditioning, Animal/physiology

Being as a non-pharmacological medical intervention, low-magnitude high-frequency vibration (LMHFV) has shown a positive effect on bone induction and remodeling for various muscle diseases in animal studies, among which dental implants osteointegration were reported to be improved as well. However, whether LMHFV can be clinically used in dental implant is still unknown. In this study, efficacy, parameters and side effects of LMHFV were analyzed via data before 15th July 2020, collecting from MEDLINE/PubMed, Embase, Ovid and Cochrane Library databases. In the screened 1,742 abstracts and 45 articles, 15 animal studies involving 972 implants were included. SYRCLE's tool was performed to assess the possible risk of bias for each study. The GRADE approach was applied to evaluate the quality of evidence. Random effects meta-analysis detected statistically significant in total BIC (P < 0.0001) and BV/TV (P = 0.001) upon loading LMHFV on implants. To conclude, LMHFV played an active role on BIC and BV/TV data according to the GRADE analysis results (medium and low quality of evidence). This might illustrate LMHFV to be a worthy way in improving osseointegration clinically, especially for osteoporosis.

Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO, identifier: NCT02612389

• dental implant
• low-magnitude high-frequency vibration
• osseointegration
• osteoporosis
• systematic review and meta-analysis

For decades, the osteogenic effect from different physical activities on bone in rodents remained uncertain. This literature review presents for the first time the effects on five exercise models (treadmill running, wheel running, swimming, resistance training and vibration modes) in three different experimental rat groups (males, females, osteopenic) on bone quality. The bone parameters presented are bone mineral density, micro-architectural and mechanical properties, and osteoblast/osteocyte and osteoclast parameters. This review shows that physical activities have a positive effect (65% of the results) on bone status, but we clearly observed a difference amongst the different protocols. Even if treadmill running is the most used protocol, the resistance training constitutes the first exercise model in term of osteogenic effects (87% of the whole results obtained on this model). The less osteogenic model is the vibration mode procedure (31%). It clearly appears that the gender plays a role on the bone response to swimming and wheel running exercises. Besides, we did not observe negative results in the osteopenic population with impact training, wheel running and vibration activities. Moreover, about osteoblast/osteocyte parameters, we conclude that high impact and resistance exercise (such jumps and tower climbing) seems to increase bone formation more than running or aerobic exercise. Among the different protocols, literature has shown that the treadmill running procedure mainly induces osteogenic effects on the viability of the osteocyte lineage in both males and females or ovariectomized rats; running in voluntary wheels contributes to a negative effect on bone metabolism in older male models; whole-body vertical vibration is not an osteogenic exercise in female and ovariectomized rats; whereas swimming provides controversial results in female models. For osteoclast parameters only, running in a voluntary wheel for old males, the treadmill running program at high intensity in ovariectomized rats, and the swimming program in a specific ovariectomy condition have detrimental consequences.

• bone macro and microarchitecture
• bone quality
• mechanical properties
• osteocyte/osteoclast
• physical exercise
• rats

The inflammatory bowel diseases (IBD), Crohn’s disease (CD) and ulcerative colitis (UC) are chronic, immune-mediated disorders of the digestive tract. IBD is considered to be a risk factor for developing osteoporosis; however current literature on this matter is inconsistent.

To assess prevalence and development of osteoporosis and low bone mineral density (BMD), and its risk factors, in IBD patients.

Systematic review of population-based studies. Studies were identified by electronic (January 2018) and manual searches (May 2018). Databases searched included EMBASE and PubMed and abstracts from 2014-2018 presented at the United European Gastroenterology Week, the European Crohn’s and Colitis Organisation congress, and Digestive Disease Week were screened. Studies were eligible for inclusion if they investigated either the prevalence of osteoporosis or osteopenia and/or risk factors for osteoporosis or low BMD in IBD patients. Studies on children under the age of 18 were excluded. Only population-based studies were included. All risk factors for osteoporosis and low BMD investigated in any included article were considered. Study quality and the possibility of bias were analysed using the Newcastle-Ottawa scale.

Twelve studies including 3661 IBD patients and 12789 healthy controls were included. Prevalence of osteoporosis varied between 4%-9% in studies including both CD and UC patients; 2%-9% in studies including UC patients, and 7%-15% in studies including CD patients. Among healthy controls, prevalence of osteoporosis was 3% and 10% in two studies. CD diagnosis, lower body mass index (BMI), and lower body weight were risk factors associated with osteoporosis or low BMD. Findings regarding gender showed inconsistent results. CD patients had an increased risk for osteoporosis or low BMD over time, while UC patients did not. Increased age was associated with decreased BMD, and there was a positive association between weight and BMI and BMD over time. Great heterogeneity was found in the included studies in terms of study methodologies, definitions and the assessment of osteoporosis, and only a small number of population-based studies was available.

This systematic review found a possible increase of prevalence of osteoporosis in CD cohorts when compared to UC and cohorts including both disease types. Lower weight and lower BMI were predictors of osteoporosis or low BMD in IBD patients. The results varied considerably between studies.

• Inflammatory bowel disease
• Osteoporosis
• Systematic review
• Epidemiology
• Bone mineral density

• Bone Density
• Child
• Colitis, Ulcerative/epidemiology
• Humans
• Inflammatory Bowel Diseases/complications
• Inflammatory Bowel Diseases/epidemiology
• Osteoporosis/diagnostic imaging
• Osteoporosis/epidemiology
• Prevalence
• Risk Factors

• PhysioMechanics
• amyotrophic lateral sclerosis
• gravity conditions
• human locomotion
• monitor training
• multiple sclerosis
• nordic walking

• IK2 RX001854 RRD VA

The use of human bone marrow mesenchymal stem cells (hBMSCs) as a tissue engineering application for individuals affected by osteoporosis and other types of bone loss diseases has been well studied in recent years. The osteogenic differentiation of hBMSCs can be regulated by a number of cues. MicroRNAs (miRNAs/miRs) serve as the key regulators of various biological processes; however, to the best of our knowledge, no information exists with regards to the specific modulatory effects of miR-10a-5p on osteogenic differentiation of hBMSCs. The aim of the present study was to investigate the relationship between hBMSCs and miR-10a-5p and, ultimately, to determine how miR-10a-5p affects the osteogenic differentiation process of hBMSCs in vitro and in vivo. The hBMSCs used in the present study were transfected with mirVana™ miRNA inhibitors and mimics, and transfection efficiency was assessed by fluorescence microscopy and reverse transcription-quantitative PCR (RT-qPCR). Viability of hBMSCs following transfection was analyzed using a Cell Counting Kit-8 assay. The mRNA expression levels of specific osteoblast markers, including alkaline phosphatase (ALP) and runt-related transcription factor 2 (RUNX2) were measured using RT-qPCR and western blot analysis. New bone formation was evaluated by Goldner's trichrome staining and micro-CT analysis in vivo. No significant difference in cell viability was observed among the different groups 24 h post-transfection. Overexpression of miR-10a-5p inhibited the expression of osteoblast makers in hBMSCs, whereas inhibition of miR-10a-5p upregulated the expression of ALP and RUNX2 in vitro. Furthermore, miR-10a-5p acted as a suppressor during the process of new bone formation in vivo. In conclusion, the findings of the present study suggested that miR-10a-5p served as a negative regulatory factor during osteoblast differentiation of hBMSCs and may be utilized in a treatment approach for bone repair in osteogenic-related diseases.

• human bone marrow mesenchymal stem cells
• micrornas
• osteogenic differentiation
• mir-10a-5p

Bones as an alive organ consist of about 70% mineral and 30% organic component. About 200 million people are suffering from osteopenia and osteoporosis around the world. There are multiple ways of protecting bone from endogenous and exogenous risk factors. Planned physical activity is another useful way for protecting bone health. It has been investigated that arranged exercise would effectively regulate bone metabolism. Until now, a number of systems have discovered how exercise could help bone health. Previous studies reported different mechanisms of the effect of exercise on bone health by modulation of bone remodeling. However, the regulation of RANKL/RANK/OPG pathway in exercise and physical performance as one of the most important remodeling systems is not considered comprehensive in previous evidence. Therefore, the aim of this review is to clarify exercise influence on bone modeling and remodeling, with a concentration on its role in regulating RANKL/RANK/OPG pathway.

• ALP, Alkaline phosphatase
• ActD, Actinomycin D
• AzadC, 5-Aza-2′-deoxycytidine
• BRD2
• BRD2, Bromodomain-containing protein 2
• CO2, Carbon Dioxide
• ChIP, Chromatin immunoprecipitation
• DAPI, 4′,6-diamidino-2-phenylindole
• DMEM, Dulbecco's Modified Eagle Medium
• DNA, Deoxyribonucleic Acid
• Epigenetics
• FACS, Fluorescence-activated cell sorting
• FCS, Fetal calf serum
• GAPDH, Glyceraldehyde 3-Phosphate Dehydrogenase
• HDAC, Histone deacetylase
• HPRT, Hypoxanthine Phosphoribosyltransferase 1
• IU, International unit
• IgG, Immunoglobulin G
• Ki-67, Antigen KI-67
• Mechanical strain
• OPG, Osteoprotegerin/tumour necrosis factor receptor superfamily member 11B
• PBS, Phosphate-Buffered Saline
• PCR, polymerase chain reaction
• PGE2, Prostaglandin E2
• RANKL/TNFSF11, receptor activator of nuclear factor-κB ligand
• RNA, Ribonucleic Acid
• RT-qPCR, Quantitative reverse transcription polymerase chain reaction
• RUNX2
• RUNX2, Runt-related transcription factor 2
• Receptor activator of nuclear factor-κB ligand
• SOST, Sclerostin
• Sclerostin
• eGFP, enhanced green fluorescent protein
• sh, Short hairpin
• β2MG, Beta-2-Microglobulin

We aimed to evaluate whether applying low magnitude vibration (LMV) in early postmenopausal osteoporosis (PMO) suppresses its progression, and to investigate underlying mechanisms. Rats were randomly divided into Sham (Sham-operated), Sham+V, OVX (ovariectomized), OVX+E2 (estradiol benzoate), OVX+V (LMV at 12–20 weeks postoperatively), and OVX+Vi (LMV at 1–20 weeks postoperatively) groups. LMV was applied for 20 min once daily for 5 days weekly. V rats were loaded with LMV at 12–20 weeks postoperatively. Vi rats were loaded with LMV at 1–20 weeks postoperatively. Estradiol (E2) rats were intramuscularly injected at 12–20 weeks postoperatively once daily for 3 days. The bone mineral densities (BMDs), biomechanical properties, and histomorphological parameters of tibiae were analyzed. In vitro, rat bone marrow-derived mesenchymal stem cells (rBMSCs) were subjected to LMV for 30 min daily for 5 days, or 17β-E2 with or without 1-day pretreatment of estrogen receptor (ER) inhibitor ICI 182,780 (ICI). The mRNA and protein expresion were performed. Data showed that LMV increased BMD, bone strength, and bone mass of rats, and the effects of Vi were stronger than those of E2. In vitro, LMV up-regulated the mRNA and protein expressions of Runx2, Osx, Col I, and OCN and down-regulated PPARγ, compared with E2. The effects of both LMV and E2 on rBMSCs were inhibited by ICI. Altogether, LMV in early PMO suppresses its progression, which is associated with osteogenic differentiation of rBMSCs via up-regulation of ERα and activation of the canonical Wnt pathway. LMV may therefore be superior to E2 for the suppression of PMO progression.

• ERα
• Wnt
• low magnitude vibration
• postmenopausal osteoporosis
• rat bone marrow-derived mesenchymal stem cells

• articular cartilage
• diet
• functional food
• immunohistochemistry
• morphology
• vitamin D

• body height
• bone density
• cheese
• children
• dairy product
• growth and development
• milk
• yogurt

• Adolescent
• Adolescent Health
• Animals
• Bone Density/drug effects
• Bone and Bones/drug effects
• Calcium, Dietary/pharmacology
• Child
• Child Health
• Dairy Products
• Diet
• Dietary Proteins/pharmacology
• Feeding Behavior
• Humans
• Milk/chemistry
• Vitamin D/pharmacology
• Vitamins

The OPG/RANK/RANKL signaling is a new family of bone metabolism biomarkers belonging to the immune system. However, the bone metabolism response to long-term exercise in the RANKL/RANK/OPG signaling is less evident. The purpose of this study was to examine these biomarkers in healthy college females after 12-weeks combined exercise intervention.

Participants (N=22, 22.4±1.3yrs) were randomly divided in two different group: 12 in the control group and 10 in the exercise group performing combined exercise program that interventions was conducted 3 times per week for 12 weeks. The outcome measures included serum concentrations of RANKL, OPG and bone metabolic cytokines such as TNF-α and IL-6, and mRNA expressions of same variables from PBMC. VO_2max and bone mineral density (BMD) were measured at before and after exercise intervention.

There were no significant differences in the serum RANKL, OPG concentrations and all RANKL/RANK/OPG signaling mRNA expression on interaction effect between group and time (NS). Also no significant differences were found in the serum TNF-α and IL-6 concentrations and mRNA expression (NS). The IL-6 mRNA expression only showed significant difference in the main effect of groups (p<.05). There were also no significant differences in the VO_2max and BMD on interaction effect between group and time (NS).

These results suggested that there were no effects on bone mineral density and RANKL/RANK/OPG signaling without the effect of 8-weeks combined exercise on cardiovascular endurance fitness.

• RANKL

As most of the existing whole-body vibration (WBV) training programs provide vertical or rotatory vibration, studies on the effects of horizontal vibration have rarely been reported. The present study was conducted to investigate the effect of WBV in the horizontal direction on balance and gait ability in chronic stroke survivors.

This study was designed as a randomized controlled trial. Twenty-one stroke survivors were randomly allocated into 2 groups (whole-body vibration group [n=9] and control group [n=12]). In the WBV group, WBV training in the horizontal direction was conducted for 6 weeks, and a conventional rehabilitation for 30 min, 3 days per week for a 6-week period, was conducted in both the WBV and control groups. Outcome variables included the static balance and gait ability measured before training and after 6 weeks.

On comparing the outcome variables before and after training in the WBV group, significant differences were observed in the cadence and single support time of gait ability. However, there were no significant differences in other variables, including velocity, step length, stride length, and double support time. In addition, after training, no significant differences in all variables were observed between the 2 groups.

The results of this study suggest that WBV training in the horizontal direction has few positive effects on balance and gait function in chronic stroke survivors. However, further investigation is needed to confirm this.

The aim of this meta-analysis was to evaluate the efficacy of Tai chi (TC) as an adjuvant treatment for osteopenia and primary osteoporosis.

We went through eight databases to identify relevant randomized controlled trials that compared TC with a control group. The primary outcome was osteoporosis-related fractures (fracture incidence). Meta-analyses and trial sequential analyses (TSA) were conducted using RevMan 5.3 and TSA 0.9.

Fifteen randomized controlled trials involving a total of 857 patients were included in the analyses. No trials reported primary outcome; however, bone mineral density (BMD) values differed significantly in subgroup 1 (TC vs no treatment; weighted mean difference [WMD] =0.05 g/cm², 95% CI 0.03 to 0.07; P<0.00001; P for heterogeneity =0.22, I²=22%) and subgroup 2 (TC vs conventional treatments; WMD =0.16 g/cm², 95% CI 0.11 to 0.21; P<0.00001; P for heterogeneity =0.008, I²=75%). In addition, two trials compared TC with conventional treatments, which found a significant difference in bone gla protein (standardized mean difference =−1.18, 95% CI −1.66 to −0.70; P<0.00001; P for heterogeneity =0.58, I²=75%). The results of the BMD were confirmed by TSA. Also, TC may have a certain effect on the relief of osteoporotic pain (WMD = −2.61, 95% CI −3.51 to −1.71; WMD = −1.39, 95% CI −2.01 to −0.77). However, it did not promote the quality of life, level of serum calcium, serum phosphorus, and also had no effect on bone turnover markers.

Although there is no study monitoring fracture incidence, TC may be beneficial for patients in improving BMD values, level of bone gla protein, and relieving osteoporotic pain. However, due to the low methodological quality, current evidence for treating osteopenia and primary osteoporosis through TC is insufficient.

• Tai chi
• evidence based medicine
• osteopenia
• primary osteoporosis
• trial sequential analyses

• DXA
• bone
• diet
• exercise
• protein

• exenatide
• insulin sensitivity
• islet cell transplantation
• leptin
• receptor activator of nuclear factor kappa-B ligand (RANKL)
• type 1 diabetes

• Biomarkers/analysis
• Blood Glucose/analysis
• Clinical Trials, Phase I as Topic
• Diabetes Mellitus, Type 1/drug therapy
• Diabetes Mellitus, Type 1/surgery
• Female
• Follow-Up Studies
• Glucose Tolerance Test
• Glycated Hemoglobin/analysis
• Homeostasis
• Humans
• Hypoglycemic Agents/therapeutic use
• Insulin/therapeutic use
• Insulin Resistance
• Islets of Langerhans Transplantation
• Longitudinal Studies
• Male
• Middle Aged
• Prognosis

• K12 HD055892 NICHD NIH HHS
• UL1 RR029879 NCRR NIH HHS
• UL1 TR002003 NCATS NIH HHS

• Inflammation
• Lubricin
• Muscle atrophy
• Olive leaf extract
• Olive oil
• Osteoarthritis
• Physical activity

• accidental falls
• exercise
• fractures
• meta-analysis
• wbv
• whole-body vibration

• Accidental Falls/prevention & control
• Aged
• Aged, 80 and over
• Bone Density
• Bone and Bones/injuries
• Bone and Bones/metabolism
• Bone and Bones/pathology
• Exercise
• Exercise Therapy
• Female
• Fractures, Bone/etiology
• Fractures, Bone/prevention & control
• Humans
• Male
• Middle Aged
• Osteoporosis, Postmenopausal
• Vibration

• R01 AG025489 NIA NIH HHS

Hydrogen sulfide (H₂S) is a gas signaling molecule that has multiple influences on physiological and pathological processes in the mammalian body, including vasodilation, neurotransmission, inflammation, hypoxia sensing and bone remodeling. Our previous studies suggested that H₂S might be involved in the periodontal tissue remodeling during the orthodontic tooth movement (OTM) via increasing periodontal ligament cell differentiation, tissue mineralization, bone formation and collagen synthesis. The aim of the present study was to investigate the effects of H₂S on alveolar bone remodeling that is associated with tooth movement. Experiments were performed in an OTM mouse model. Sodium hydrosulfide (NaHS), which is a donor of H₂S and DL-propargylglycine (PAG) and a cystathionine-γ-lyase (CSE) inhibitor, which could also decrease H₂S expression, were administered intraperitoneally and respectively. A total of 60 male C57BL6/J mice were divided into 4 groups; Control, NaHS, PAG and combination (PAG+NaHS). The rate of OTM and the bone mineral density (BMD) of alveolar bone were scanned and measured by micro-computed tomography (micro-CT). The number of osteoclasts and expression of the tumor necrosis factor ligand superfamily member-11 (RANKL), alkaline phosphatase (ALP), osteocalcin (OCN) and osteoprotegerin (OPG) in alveolar bone were accessed to evaluate the osteoclastic activity and osteogenesis with histochemistry of tartrate-resistant acid phosphatase staining, immunohistochemistry and reverse transcription-quantitative polymerase chain reaction. In the alveolar bone, NaHS increased the OTM and decreased the BMD, respectively. PAG significantly decrease OTM and increased the BMD. NaHS combined with PAG rescued the PAG-induced changes in the OTM and the BMD. Additionally, the number of osteoclasts, the expression of RANKL, ALP, OCN and the ratio of RANKL/OPG were significantly up-regulated in the NaHS group. In contrast, PAG down-regulated the number of osteoclasts, the expression of RANKL, ALP, OCN and the ratio of RANKL/OPG. These findings suggested that H₂S might facilitate the OTM by enhancing alveolar bone remodeling as a result of an increased osteoclastic activity and osteogenesis.

• Adaptation, Physiological
• Adaptive Immunity
• Animals
• Autophagy
• Exercise/physiology
• Exercise Therapy
• Humans
• Immunity, Innate
• Mice
• Muscle, Skeletal/blood supply
• Muscle, Skeletal/immunology
• Muscle, Skeletal/metabolism
• Neoplasms/immunology
• Neoplasms/physiopathology
• Neoplasms/therapy
• Neovascularization, Pathologic/physiopathology
• Neovascularization, Physiologic
• Physical Conditioning, Animal/physiology
• Tumor Microenvironment/physiology

• P30 CA008748 NCI NIH HHS

• Biomechanics
• Bone regeneration
• Bone remodelling
• Bone volume (BV)
• Fracture healing
• Histology
• Micro-CT (μCT)
• Tissue mineral density (TMD)

Osteoarthritis is the most common human arthritis characterized by degeneration of articular cartilage. Several studies reported that levels of human cartilage glycoprotein chitinase 3-like-1 (CHI3L1) are known as a potential marker for the activation of chondrocytes and the progression of Osteoarthritis (OA), whereas lubricin appears to be chondroprotective. The aim of this study was to investigate the co-expression and co-localization of CHI3L1 and lubricin in normal and osteoarthritic rat articular cartilage to correlate their modified expression to a specific grade of OA. Samples of normal and osteoarthritic rat articular cartilage were analyzed by the Kellgren–Lawrence OA severity scores, the Kraus’ modified Mankin score and the Histopathology Osteoarthritis Research Society International (OARSI) system for histomorphometric evaluations, and through CHI3L1 and lubricin gene expression, immunohistochemistry and double immuno-staining analysis. The immunoexpression and the mRNA levels of lubricin increased in normal cartilage and decreased in OA cartilage (normal vs. OA, p < 0.01). By contrast, the immunoexpression and the mRNA levels of CHI3L1 increased in OA cartilage and decreased in normal cartilage (normal vs. OA, p < 0.01). Our findings are consistent with reports suggesting that these two glycoproteins are functionally associated with the development of OA and in particular with grade 2/3 of OA, suggesting that in the future they could be helpful to stage the severity and progression of the disease.

• CHI3L1
• Immunohistochemistry
• Lubricin
• Osteoarthritis
• anterior cruciate ligament transection (ACLT)
• mRNA

• apoptosis
• autophagy
• biomarker
• chondrocyte death
• osteoarthritis (OA)

Osteoarthritis (OA) is a growing public health problem across the globe, affecting more than half of the over 65 population. In the past, OA was considered a wear and tear disease, leading to the loss of articular cartilage and joint disability. Nowadays, thanks to advancements in molecular biology, OA is believed to be a very complex multifactorial disease. OA is a degenerative disease characterized by “low-grade inflammation” in cartilage and synovium, resulting in the loss of joint structure and progressive deterioration of cartilage. Although the disease can be dependent on genetic and epigenetic factors, sex, ethnicity, and age (cellular senescence, apoptosis and lubricin), it is also associated with obesity and overweight, dietary factors, sedentary lifestyle and sport injuries. The aim of this review is to highlight how certain behaviors, habits and lifestyles may be involved in the onset and progression of OA and to summarize the principal risk factors involved in the development of this complicated joint disorder.

• Cartilage, Articular/metabolism
• Cartilage, Articular/pathology
• Diet
• Disease Progression
• Epigenesis, Genetic
• Humans
• Life Style
• Motor Activity
• Osteoarthritis/genetics
• Osteoarthritis/metabolism
• Osteoarthritis/pathology
• Reactive Oxygen Species/metabolism
• Risk Factors

• 20194 Arthritis Research UK

Osteoarthritis (OA) is a major health problem in the increasingly elderly population. Therefore, it is crucial to prevent and treat OA at an early stage. The present study investigated whether pamidronate disodium (PAM), a bone-loss inhibitor, can significantly prevent or reverse the progression of early anterior cruciate ligament transection (ACLT)-induced OA. Whether therapeutic intervention is associated with regulation of the expression of osteoprotegerin (OPG), receptor activator of nuclear factor-κB ligand (RANKL), metalloproteinase-9 (MMP-9) or Toll-like receptor-4 (TLR-4) in cartilage and/or subchondral bone was also investigated.

60 New Zealand rabbits were randomized into four groups: Sham-operated (n = 20); ACLT (n = 20); short-term treatment with PAM (PAM-S, n = 10) and long-term treatment with PAM (PAM-L, n = 10). For cartilage and subchondral bone testing, rabbits from Sham and ACLT groups were harvested at 2, 4, 6, and 14 weeks. Rabbits were given PAM from the 4th week after ACLT operation in PAM-S and PAM-L group, and were harvested at 6 and 14 weeks, respectively. Trabecular characteristics and cartilage changes were detected using Micro-CT, safranin O and rapid green staining, respectively. Immunohistochemical staining for OPG and RANKL were also performed. OPG, RANKL, MMP-9 and TLR-4 expression was evaluated by western blot analysis.

Micro-CT and histology analyses indicated that PAM treatment for 2 or 10 weeks could completely prevent or reverse osteoarthritic subchondral bone loss and cartilage surface erosion. Immunohistochemistry and western blot analysis indicated that expression of OPG and RANKL increased, although RANKL expression increased more significantly than that of OPG. Therefore the ratio of OPG to RANKL was lower in the ACLT group. However, the ratio of OPG to RANKL in the PAM group was significantly higher than that in the ACLT group. Additionally, expression of MMP-9 and TLR-4 were upregulated in the ACLT group and downregulated in the PAM treated groups.

PAM can significantly inhibit and even reverse early osteoarthritic subchondral bone loss, thus alleviating the process of cartilaginous degeneration. The mechanisms involved may be associated with the upregulation of OPG expression, and downregulation of RANKL, MMP-9 and TLR-4 expression.

The online version of this article (doi:10.1186/1471-2474-15-370) contains supplementary material, which is available to authorized users.

Osteoarthritis is a degenerative joint disease, which affects millions of people around the world. It occurs when the protective cartilage at the end of bones wears over time, leading to loss of flexibility of the joint, pain and stiffness. The cause of osteoarthritis is unknown, but its development is associated with different factors, such as metabolic, genetic, mechanical and inflammatory ones. In recent years the biological role of chitinases has been studied in relation to different inflammatory diseases and more in particular the elevated levels of human cartilage glycoprotein 39 (CHI3L1) and chitotriosidase (CHIT1) have been reported in a variety of diseases including chronic inflammation and degenerative disorders. The aim of this study was to investigate, by immunohistochemistry, the distribution of CHI3L1 and CHIT1 in osteoarthritic and normal rat articular cartilage, to discover their potential role in the development of this disease. The hypothesis was that the expression of chitinases could increase in OA disease. Immunohistochemical analysis showed that CHI3L1 and CHIT1 staining was very strong in osteoarthritic cartilage, especially in the superficial areas of the cartilage most exposed to mechanical load, while it was weak or absent in normal cartilage. These findings suggest that these two chitinases could be functionally associated with the development of osteoarthritis and could be used as markers, so in the future they could have a role in the daily clinical practice to stage the severity of the disease. However, the longer-term in vivoand in vitro studies are needed to understand the exact mechanism of these molecules, their receptors and activities on cartilage tissue.

• Exercise
• Osteoarthritis
• Rehabilitation

In this review article, we describe benefits and disadvantages of the established histochemical methods for studying articular cartilage tissue under normal, pathological and experimental conditions. We illustrate the current knowledge on cartilage tissue based on histological and immunohistochemical aspects, and in conclusion we provide a short overview on the degeneration of cartilage, such as osteoarthritis. Adult articular cartilage has low capacity to repair itself, and thus even minor injuries may lead to progressive damage and osteoarthritic joint degeneration, resulting in significant pain and disability. Numerous efforts have been made to implement the knowledge in the study of cartilage in the last years, and histochemistry proved to be an especially powerful tool to this aim.

• Bone strength
• Immobilization
• Osteoporosis
• Propranolol
• Rat model

• Animals
• Caspase 3/metabolism
• Chondrocytes/pathology
• Growth Plate/metabolism
• Growth Plate/pathology
• Immunohistochemistry
• Interleukin-6/metabolism
• Poly(ADP-ribose) Polymerases/metabolism
• Rats
• Rats, Sprague-Dawley
• Salter-Harris Fractures
• Tumor Necrosis Factor-alpha/metabolism