Identification of potential specific biomarkers and key signaling pathways between osteogenic and adipogenic differentiation of hBMSCs for osteoporosis therapy

Journal of Orthopaedic Surgery and Research

Bikang Zhu¹  Zhenhui Lu¹  Li Zheng¹  Xixi He²  Jianjun Wu²  Zhi Zhang²  Peian Cai²  Jinmin Zhao³ 

[1] Guangxi Engineering Center in Biomedical Material for Tissue and Organ Regeneration, The First Affiliated Hospital of Guangxi Medical University, 530021, Nanning, China;Guangxi Collaborative Innovation Center for Biomedicine, The First Affiliated Hospital of Guangxi Medical University, 530021, Nanning, China;Guangxi Engineering Center in Biomedical Material for Tissue and Organ Regeneration, The First Affiliated Hospital of Guangxi Medical University, 530021, Nanning, China;Guangxi Collaborative Innovation Center for Biomedicine, The First Affiliated Hospital of Guangxi Medical University, 530021, Nanning, China;Department of Orthopaedics Trauma and Hand Surgery, The First Affiliated Hospital of Guangxi Medical University, 530021, Nanning, China;Guangxi Engineering Center in Biomedical Material for Tissue and Organ Regeneration, The First Affiliated Hospital of Guangxi Medical University, 530021, Nanning, China;Guangxi Collaborative Innovation Center for Biomedicine, The First Affiliated Hospital of Guangxi Medical University, 530021, Nanning, China;Department of Orthopaedics Trauma and Hand Surgery, The First Affiliated Hospital of Guangxi Medical University, 530021, Nanning, China;Guangxi Key Laboratory of Regenerative Medicine, The First Affiliated Hospital of Guangxi Medical University, 530021, Nanning, China;

关键词: Osteoporosis;    Osteogenesis;    Adipogenesis;    Bone marrow mesenchymal stem cells;    Microarray analyses;   

DOI  :  10.1186/s13018-020-01965-3

来源: Springer

【 摘 要 】

BackgroundThe differentiation of bone mesenchymal stem cells (BMSCs) into adipogenesis (AD) rather than osteogenesis (OS) is an important pathological feature of osteoporosis. Illuminating the detailed mechanisms of the differentiation of BMSCs into OS and AD would contribute to the interpretation of osteoporosis pathology.MethodsTo identify the regulated mechanism in lineage commitment of the BMSCs into OS and AD in the early stages, the gene expression profiles with temporal series were downloaded to reveal the distinct fates when BMSCs adopt a committed lineage. For both OS and AD lineages, the profiles of days 2–4 were compared with day 0 to screen the differentially expressed genes (DEGs), respectively. Next, the functional enrichment analysis was utilized to find out the biological function, and protein-protein interaction network to predict the central genes. Finally, experiments were performed to verify our finding.ResultsFoxO signaling pathway with central genes like FoxO3, IL6, and CAT is the crucial mechanism of OS, while Rap1 signaling pathway of VEGFA and FGF2 enrichment is more significant for AD. Besides, PI3K-Akt signaling pathway might serve as the latent mechanism about the initiation of differentiation of BMSCs into multiple lineages.ConclusionAbove hub genes and early-responder signaling pathways control osteogenic and adipogenic fates of BMSCs, which maybe mechanistic models clarifying the changes of bone metabolism in the clinical progress of osteoporosis. The findings provide a crucial reference for the prevention and therapy of osteoporosis.

【 授权许可】

CC BY