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
Abstract
BACKGROUND

Osteoporosis is a common metabolic bone disorder induced by an imbalance between osteoclastic activity and osteogenic activity. During osteoporosis, bone mesenchymal stem cells (BMSCs) exhibit an increased ability to differentiate into adipocytes and a decreased ability to differentiate into osteoblasts, resulting in bone loss. Jumonji domain-containing 1C (JMJD1C) has been demonstrated to suppress osteoclastogenesis.

AIM

To examine the effect of JMJD1C on the osteogenesis of BMSCs and the potential underlying mechanism.

METHODS

BMSCs were isolated from mouse bone marrow tissues. Oil Red O staining, Alizarin red staining, alkaline phosphatase staining and the expression of adipogenic and osteogenic-associated genes were assessed to determine the differentiation of BMSCs. Bone marrow-derived macrophages (BMMs) were incubated with receptor activator of nuclear factor-kappa Β ligand to induce osteoclast differentiation, and osteoclast differentiation was confirmed by tartrate-resistant acid phosphatase staining. Other related genes were measured via reverse transcription coupled to the quantitative polymerase chain reaction and western blotting. Enzyme-linked immunosorbent assays were used to measure the levels of inflammatory cytokines, including tumor necrosis factor alpha, interleukin-6 and interleukin-1 beta.

RESULTS

The osteogenic and adipogenic differentiation potential of BMSCs isolated from mouse bone marrow samples was evaluated. JMJD1C mRNA and protein expression was upregulated in BMSCs after osteoblast induction, while p-nuclear factor-κB (NF-κB) and inflammatory cytokines were not significantly altered. Knockdown of JMJD1C repressed osteogenic differentiation and enhanced NF-κB activation and inflammatory cytokine release in BMSCs. Moreover, JMJD1C expression decreased during BMM osteoclast differentiation.

CONCLUSION

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

Keywords: Osteoporosis; Mesenchymal stem cells; Osteogenesis; Jumonji domain-containing 1C; Nuclear factor-κB

Core Tip: Jumonji domain-containing 1C (JMJD1C) is a marker gene for osteoporosis disease. JMJD1C promotes osteogenic differentiation of bone mesenchymal stem cells (BMSCs). JMJD1C inhibited osteoclast differentiation of bone marrow-derived macrophages. JMJD1C knockdown promotes nuclear factor-κB activation in BMSCs during osteogenic differentiation.