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Bone marrow adiposity during pathologic bone loss: molecular mechanisms underlying the cellular events

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Abstract

Bone marrow (BM) is a heterogeneous niche where bone marrow stromal cells (BMSCs), osteoblasts, osteoclasts, adipocytes, hematopoietic cells, and immune cells coexist. The cellular composition of BM changes with various pathophysiological states. A reduction in osteoblast number and a concomitant increase in adipocyte number in aging and pathological conditions put bone marrow adipose tissue (BMAT) into spotlight. Accumulating evidence strongly supports that an overwhelming production of BMAT is a major contributor to bone loss disorders. Therefore, BMAT-targeted therapy can be an efficient and feasible intervention for osteoporosis. However, compared to blocking bone-destroying molecules produced by BMAT, suppressing BMAT formation is theoretically a more effective and fundamental approach in treating osteoporotic bone diseases. Thus, a deep insight into the molecular basis underlying increased BM adiposity during pathologic bone loss is critical to formulate strategies for therapeutically manipulating BMAT. In this review, we comprehensively summarize the molecular mechanisms involved in adipocyte differentiation of BMSCs as well as the interaction between bone marrow adipocytes and osteoclasts. More importantly, we further discuss the potential clinical implications of therapeutically targeting the upstream of BMAT formation in bone loss diseases.

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Funding

This work was supported by the National Natural Science Foundation of China (No. 81770875); the Post-Doctor Research Project, West China Hospital, Sichuan University (No.19HXBH053); the Health and Family Planning Commission of Sichuan Province (No. 19PJ096); and the 1.3.5 project for discipline of excellence, West China Hospital, Sichuan University (No. 2020HXFH008, No. ZYJC18003).

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  1. Department of Endocrinology and Metabolism, Laboratory of Endocrinology and Metabolism, Rare Disease Center, West China Hospital, Sichuan University, No.37 Guoxue Alley, Wuhou District, Chengdu, 610041, Sichuan Province, China

    Jiao Li, Lingyun Lu & Xijie Yu

  2. Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, 610041, China

    Lingyun Lu

  3. Department of Rheumatology and Immunology, Rare Disease Center, West China Hospital, Sichuan University, Chengdu, 610041, China

    Yi Liu

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Xijie Yu provided the conception of the manuscript. Jiao Li and Lingyun Lu performed the literature search and drafted the work. Yi Liu revised the manuscript. All authors read and approved the final manuscript.

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Li, J., Lu, L., Liu, Y. et al. Bone marrow adiposity during pathologic bone loss: molecular mechanisms underlying the cellular events. J Mol Med 100, 167–183 (2022). https://doi.org/10.1007/s00109-021-02164-1

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  • DOI: https://doi.org/10.1007/s00109-021-02164-1

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