1. Academic Validation
  2. A mechanosensitive lipolytic factor in the bone marrow promotes osteogenesis and lymphopoiesis

A mechanosensitive lipolytic factor in the bone marrow promotes osteogenesis and lymphopoiesis

  • Cell Metab. 2022 Aug 2;34(8):1168-1182.e6. doi: 10.1016/j.cmet.2022.05.009.
Hui Peng 1 Biao Hu 1 Ling-Qi Xie 1 Tian Su 1 Chang-Jun Li 1 Ya Liu 1 Mi Yang 1 Ye Xiao 1 Xu Feng 1 Rui Zhou 1 Qi Guo 1 Hai-Yan Zhou 1 Yan Huang 1 Tie-Jian Jiang 1 Xiang-Hang Luo 2
Affiliations

Affiliations

  • 1 Department of Endocrinology, Endocrinology Research Center, Xiangya Hospital of Central South University, Changsha, Hunan 410008, China.
  • 2 Department of Endocrinology, Endocrinology Research Center, Xiangya Hospital of Central South University, Changsha, Hunan 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan 410008, China; Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Hunan 410008, China. Electronic address: xianghangluo@sina.com.
Abstract

Exercise can prevent osteoporosis and improve immune function, but the mechanism remains unclear. Here, we show that exercise promotes reticulocalbin-2 secretion from the bone marrow macrophages to initiate bone marrow fat lipolysis. Given the crucial role of lipolysis in exercise-stimulated osteogenesis and lymphopoiesis, these findings suggest that reticulocalbin-2 is a pivotal regulator of a local adipose-osteogenic/immune axis. Mechanistically, reticulocalbin-2 binds to a functional receptor complex, which is composed of neuronilin-2 and Integrin beta-1, to activate a cAMP-PKA signaling pathway that mobilizes bone marrow fat via lipolysis to fuel the differentiation and function of mesenchymal and hematopoietic stem cells. Notably, the administration of recombinant reticulocalbin-2 in tail-suspended and old mice remarkably decreases bone marrow fat accumulation and promotes osteogenesis and lymphopoiesis. These findings identify reticulocalbin-2 as a novel mechanosensitive lipolytic factor in maintaining energy homeostasis in bone resident cells, and it provides a promising target for skeletal and immune health.

Keywords

bone marrow fat; bone metabolism; exercise; fat metabolism; immunity; lipolysis; reticulocalbin-2.

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