In vivo degradation of bone scaffolds is significantly influenced by osteoclast (OC) activity, which is orchestrated by the interplay between receptor activator of nuclear factor-kappa B ligand (RANKL) and osteoprotegerin (OPG). The ratio of RANKL/OPG is a crucial determinant of OC-mediated bone resorption, which plays an integral role in bone remodeling and scaffold degradation. Elevated levels of RANKL relative to OPG enhance osteoclastogenesis, thereby accelerating the degradation process essential for integrating bone scaffolds into the host tissue.

To elucidate the effects of OPG gene silencing on osteoclastogenesis within rat bone marrow-derived mesenchymal stem cells (BMSCs). By investigating these effects, the study aimed to provide deeper insights into the regulatory mechanisms that influence bone scaffold degradation, potentially leading to improved bone repair and regeneration strategies.

We employed recombinant lentiviral plasmids to silence the OPG gene in rat BMSCs to achieve the aims. The efficacy of gene silencing was assessed using quantitative reverse transcription polymerase chain reaction and western blot analysis to measure the expression levels of OPG and RANKL. Tartrate-resistant acid phosphatase staining was utilized to evaluate the formation of OCs. Additionally, co-immunoprecipitation assays were conducted to explore the interactions between RANKL and OPG proteins, further assessing the biochemical pathways involved in osteoclastogenesis.

The silencing of the OPG gene in BMSCs resulted in a significant increase in the RANKL/OPG ratio, evidenced by decreased expression levels of OPG and increased levels of RANKL. Enhanced osteoclastogenesis was observed through tartrate-resistant acid phosphatase staining, which indicated a substantial rise in OC formation in response to the altered RANKL/OPG balance. The co-immunoprecipitation assays provided concrete evidence of the direct interaction between RANKL and OPG proteins, substantiating their pivotal roles in regulating OC activity.

The findings from this study underscore the critical role of the RANKL/OPG axis in osteoclastogenesis. Silencing of the OPG gene in BMSCs effectively increases the RANKL/OPG ratio, promoting OC activity and potentially enhancing bone scaffold degradation. This regulatory mechanism offers a promising avenue for modulating bone remodeling processes, which is essential for effective bone repair and the successful integration of bone scaffolds into damaged sites. Future research might focus on optimizing the control of this axis to better facilitate bone tissue engineering and regenerative therapies.

Increasing evidence has demonstrated that non-coding RNAs, including the lncRNA MIR155HG, are involved in the pathogenesis of postmenopausal osteoporosis (PMOP). In the current study, we studied MIR155HG function in regulation of osteogenic differentiation and tried to reveal the underlying mechanisms.

Forty blood samples taken from 20 PMOP patients (PMOP group) and 20 postmenopausal individuals without osteoporosis (control group) were used to compare the contents of MIR155HG and miR-155-5p via RT-PCR. Alizarin red S staining and ALP staining were used to evaluate the osteogenic differentiation potential of bone marrow mesenchymal stem cells (BMSCs).

Elevated levels of MIR155HG and miR-155-5p were observed in the blood samples of the PMOP group. Upregulation of MIR155HG resulted in decreased expression of OPN, OSX, ALP, RUNX2 and β-catenin but increased DKK1 expression, together with decreased Alizarin red S + and ALP + staining areas. However, downregulation of DKK1 did not obviously change the above indices induced by MIR155HG upregulation. Further experiments revealed that MIR155HG caused an increase in the expression of miR-155-5p, which also serves as an inhibitor of the osteogenic differentiation of BMSCs through binding to β-catenin. Consistent with DKK1 knockdown, downregulation of miR-155-5p only also did not obviously reverse the repressive effect of MIR155HG on osteoblastic differentiation, but downregulation of DKK1 and miR-155-5p synchronously restored the osteogenic differentiation ability of BMSCs suppressed by MIR155HG overexpression.

MIR155HG suppressed the osteoblastic differentiation of BMSCs by regulating miR-155-5p and DKK1 expression. Either inhibition of miR-155-5p and DKK1 or direct suppression of MIR155HG may be effective approaches for treating PMOP.

Long noncoding RNAs (lncRNAs), as a potentially new and crucial element of biological regulation, have gained widespread attention in recent years. Our previous work identified lncRNA empty spiracles homeobox 2 antisence (EMX2-AS) was significantly increased during the osteoblast differentiation of mesenchymal stem cells (MSCs). Overexpression of lncRNA EMX2-AS promoted osteogenesis in vitro and enhanced heterotopic bone formation in vivo, whereas lncRNA EMX2-AS knockdown had the opposite effect. EMX2 could negatively regulate the osteoblast differentiation of MSCs. lncRNA EMX2-AS was 80% expressed in the cytoplasm during osteoblast differentiation in MSCs. Mechanistic analysis revealed that lncRNA EMX2-AS acts as a positive regulator of osteogenic differentiation through interaction with EMX2 and suppression of its expression at the translational level and Wnt/β-catenin pathway is involved in lncRNA EMX2-AS/EMX2 regulated osteogenic differentiation. Our findings not only provide new targets for the treatment of diseases related to osteoblast differentiation disruption but also enrich the understanding of the regulation mechanisms of lncRNA during stem cell differentiation.

In recent years, a common-used antidiabetic drug, liraglutide, was identified with extra effects on lipid metabolism. Its effects against excessive lipid deposition in bone marrow were gained much attention but not well established. Our aim in the present study is to explore the interaction of miRNAs-mRNAs altered by liraglutide administration during bone marrow adipogenesis in diabetes. To establish the diabetic animal model, rats were treated with high fat diet (HFD) and STZ injection. We then identified the lowering effect of liraglutide on lipids metabolism in the diabetes. During this process, high-throughput sequencing and bioinformatics analyses on miRNAs extracted from bone marrow mesenchymal stem cells (BMSCs) were conducted after liraglutide administration. We then identified five differentially expressed miRNAs (miRNA-150-5p, miRNA-129-5p, miRNA-201-3p, miRNA-201-5p, and miRNA-214-5p). The expressions of the DE miRNAs were verified as temporal specific expression patterns in Day 3 and in Day 7. Among them, miRNA-150-5p expression was more stable and consistent with the sequencing data. Of interest, miR-150-5p overexpression facilitated adipogenesis of BMSCs. But this promotion was alleviated by liraglutide. The predicted target gene of miR-150-5p, GDF11, was validated to be involved in liraglutide alleviated BMSCs' lipid accumulation in diabetes. In vitro, liraglutide increased the GDF11 expression, rescued its down-expression by siGDF11 and inhibit the adipogenesis of BMSCs cultured in high glucose medium. In vivo, liraglutide reversed the HFD-STZ induced excessive lipid droplets by up-regulation of GDF11 expression, which was discounted by agomiR-150-5p injection. Above all, liraglutide might alleviate bone marrow fat accumulation via inactivating miR-150-5p/GDF11 axis in diabetes.

The notion that obesity can be a protective factor for bone health is a topic of ongoing debate. Increased body weight may have a positive impact on bone health due to its mechanical effects and the production of estrogen by adipose tissue. However, recent studies have found a higher risk of bone fracture and delayed bone healing in elderly obese patients, which may be attributed to the heightened risk of bone immune regulation disruption associated with obesity. The balanced functions of bone cells such as osteoclasts, osteoblasts, and osteocytes, would be subverted by aberrant and prolonged immune responses under obese conditions. This review aims to explore the intricate relationship between obesity and bone health from the perspective of osteoimmunology, elucidate the impact of disturbances in bone immune regulation on the functioning of bone cells, including osteoclasts, osteoblasts, and osteocytes, highlighting the deleterious effects of obesity on various diseases development such as rheumatoid arthritis (RA), osteoarthritis (AS), bone fracture, periodontitis. On the one hand, weight loss may achieve significant therapeutic effects on the aforementioned diseases. On the other hand, for patients who have difficulty in losing weight, the osteoimmunological therapies could potentially serve as a viable approach in halting the progression of these disease. Additional research in the field of osteoimmunology is necessary to ascertain the optimal equilibrium between body weight and bone health.

To study the effect of miR-150-5p on the osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs), and further explore the relationship between its regulatory mechanism and irisin.

We isolated mouse BMSCs, and induced osteogenic differentiation by osteogenic induction medium. Using qPCR to detect the expression of osteogenic differentiation-related genes, western blot to detect the expression of osteogenic differentiation-related proteins, and luciferase reporter system to verify that FNDC5 is the target of miR-150-5p. Irisin intraperitoneal injection to treat osteoporosis in mice constructed by subcutaneous injection of dexamethasone.

Up-regulation of miR-150-5p inhibited the proliferation of BMSCs, and decreased the content of osteocalcin, ALP activity, calcium deposition, the expression of osteogenic differentiation genes (Runx2, OSX, OCN, OPN, ALP and BMP2) and protein (BMP2, OCN, and Runx2). And down-regulation of miR-150-5p plays the opposite role of up-regulation of miR-150-5p on osteogenic differentiation of BMSCs. Results of luciferase reporter gene assay showed that FNDC5 gene was the target gene of miR-150-5p, and miR-150-5p inhibited the expression of FNDC5 in mouse BMSCs. The expression of osteogenic differentiation genes and protein, the content of osteocalcin, ALP activity and calcium deposition in BMSCs co-overexpressed by miR-150-5p and FNDC5 was significantly higher than that of miR-150-5p overexpressed alone. In addition, the overexpression of FNDC5 reversed the blocked of p38/MAPK pathway by the overexpression of miR-150-5p in BMSCs. Irisin, a protein encoded by FNDC5 gene, improved symptoms in osteoporosis mice through intraperitoneal injection, while the inhibitor of p38/MAPK pathway weakened this function of irisin.

miR-150-5p inhibits the osteogenic differentiation of BMSCs by targeting irisin to regulate the/p38/MAPK signaling pathway, and miR-150-5p/irisin/p38 pathway is a potential target for treating osteoporosis.

The major challenges in Osteosarcoma (OS) therapy are its heterogeneity and drug resistance. The development of new therapeutic approaches to overcome the major growth mechanisms of OS is urgently needed. The search for specific molecular targets and promising innovative approaches in OS therapy, including drug delivery methods, is an urgent problem. Modern regenerative medicine focuses on harnessing the potential of mesenchymal stem cells (MSCs) because they have low immunogenicity. MSCs are important cells that have received considerable attention in cancer research. Currently, new cell-based methods for using MSCs in medicine are being actively investigated and tested, especially as carriers for chemotherapeutics, nanoparticles, and photosensitizers. However, despite the inexhaustible regenerative potential and known anticancer properties of MSCs, they may trigger the development and progression of bone tumors. A better understanding of the complex cellular and molecular mechanisms of OS pathogenesis is essential to identify novel molecular effectors involved in oncogenesis. The current review focuses on signaling pathways and miRNAs involved in the development of OS and describes the role of MSCs in oncogenesis and their potential for antitumor cell-based therapy.

Some studies suggested obesity may be beneficial in preventing bone loss through the negative relationship between body mass index (BMI) and osteoporosis in senile. However, using BMI to measure obesity is unconvincing due to confounding factors such as muscle mass were not taken into account, and few articles have yet taken a better way to evaluate the relationship between obesity and osteoporosis.

Using a cross-sectional sample of 1,979 participants aged ≥65 years from the National Health and Nutrition Examination Survey (NHANES) 2017 to 2020, we evaluated the relation of weight-adjusted waist index (WWI) with osteoporosis. WWI was calculated as waist (cm) divided by the square root of body weight (kg). Diagnosis of osteoporosis was described as follows: according to the updated reference for calculating bone mineral density T-Scores, we marked the BMD value as X, using the formula T _{femoral neck}= (X g/cm²-0.888 g/cm²)/0.121 g/cm², T _{lumbar spine}= (X g/cm²- 1.065 g/cm²)/0.122 g/cm², and defined those with a final T _{femoral neck} <-0.25. T _{lumbar spine}<-0.25 or patients with previously diagnosed OP in other hospitals as osteoporosis.

All the 1,979 participants were between 65 and 80 years, there were 379 (21.1%) with osteoporosis, 608 (30.7%) with WWI exceeding 12 (cm/√kg) (range 8.85-14.14), and 955 (48.3%) women. Furthermore, the relationship between WWI and osteoporosis was nonlinear with a threshold effect point. Odds of OP significantly increased with the increase of WWI (OR 2.33, 95% CI 11.48-3.38, P = 0.0001) at the right side of the threshold point (WWI≥12) according to the threshold effect study.

Found a significant positive relationship between WWI and osteoporosis. Body fat management in the senile may be good to prevent osteoporosis if confirmed by other prospective studies analyzing the longitudinal risk of osteoporosis with obesity.