Basic Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Feb 26, 2024; 16(2): 151-162
Published online Feb 26, 2024. doi: 10.4252/wjsc.v16.i2.151
Silencing of Jumonji domain-containing 1C inhibits the osteogenic differentiation of bone marrow mesenchymal stem cells via nuclear factor-κB signaling
Jing-Yi Li, Ting-Ting Wang, Li Ma, Yu Zhang, Di Zhu
Jing-Yi Li, Department of Medical Cosmetology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China
Ting-Ting Wang, Department of General Gerontology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
Li Ma, Department of Plastic Surgery, China-Japan Friendship Hospital, Beijing 100029, China
Yu Zhang, Senior Department of Hematology, The Fifth Medical Centre, General Hospital of Chinese People’s Liberation Army, Beijing 100071, China
Di Zhu, Department of Orthopaedic Surgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China
Author contributions: Li JY contributed independently to this work, and performed most of the research; Li JY, Wang TT, Ma L, Zhang Y, and Zhu D designed the research study; Li JY, Wang TT, Ma L, and Zhang Y contributed new reagents and analytic tools, analyzed the data and wrote and revised the manuscript; and all authors have read and approve the final manuscript.
Supported by 2018 Henan Medical Science and Technology Research Plan Project, China, No. SBGJ2018019.
Institutional review board statement: This study was approved by the Ethics Committee of Beijing Tiantan Hospital Affiliated with Capital Medical University.
Institutional animal care and use committee statement: The animal experiments were approved by the Ethics Committee of Beijing Tiantan Hospital Affiliated with Capital Medical University.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Di Zhu, MD, Academic Research, Department of Orthopaedic Surgery, Beijing Tiantan Hospital, Capital Medical University, No. 119 South 4th Ring West Road, Fengtai District, Beijing 100070, China. zhudi214@126.com
Received: November 5, 2023
Peer-review started: November 5, 2023
First decision: December 5, 2023
Revised: December 20, 2023
Accepted: January 17, 2024
Article in press: January 17, 2024
Published online: February 26, 2024
Processing time: 112 Days and 16.7 Hours
ARTICLE HIGHLIGHTS
Research background

Osteoporosis, particularly women of postmenopausal age is elicited by the disequilibrium of osteoblastic bone formation and osteoclastic bone resorption. Elucidation of the molecular mechanisms underlying osteoporosis is important for developing effective therapeutic strategies for this disease.

Research motivation

Bone mesenchymal stem cells (BMSCs) have certain characteristics of differentiation into various types of cells, such as adipocytes and osteoblasts. So that, BMSCs are playing a critical role in bone homeostasis and munch more research groups are utilizing BMSCs for the repair of bone fractures resulting from osteoporosis. The researchers found that Jumonji C domain-containing 1C (JMJD1C) deficiency results in elevated alveolar bone loss in oral inflammatory lesions and loss of JMJD1C accelerates bone marrow-derived macrophage (BMM) differentiation into osteoclasts in vitro. Database analysis revealed that JMJD1C expression is downregulated in BMSCs from patients with osteoporosis. Furthermore, researchers revealed that JMJD1C levels are increased in osteogenic induction medium and BMSC growth medium supplemented with modified extracellular matrix.

Research objectives

To investigate whether JMJD1C is involved in osteoblast differentiation of BMSCs during osteoporosis.

Research methods

We isolated BMSCs from C57/BL6 suckling mice bone marrow tissues. We assessed the differentiation of BMSCs with Oil Red O staining, Alizarin red staining, alkaline phosphatase staining and reverse transcription coupled to the quantitative polymerase chain reaction. We isolated BMMs and incubated with receptor activator of nuclear factor-kappa Β ligand to induce osteoclast differentiation. The tartrate-resistant acid phosphatase staining were used to confirm the effect of osteoclast differentiation. We used enzyme-linked immunosorbent assay to measure the levels of inflammatory cytokines, including tumor necrosis factor alpha (TNF-α), interleukin-6 (IL)-6 and IL-1β.

Research results

JMJD1C mRNA and protein expression was increased in BMSCs after osteoblast induction. Silence JMJD1C repressed osteogenic differentiation and enhanced nuclear factor-κB (NF-κB) activation and inflammatory cytokine release in BMSCs. JMJD1C upregulation decreased during BMM osteoclast differentiation.

Research conclusions

We found that the signaling pathway of JMJD1C/NF-κB is potentially involved in BMSC osteogenic differentiation and may play vital roles in the pathogenesis of osteoporosis.

Research perspectives

R&D of MSCs (BMSC, adipose-derived SC, human umbilical cord MSC and embryonic SC, etc.) and their preparations in the field of osteoporosis treatment.