A mechanosensitive lipolytic factor in the bone marrow promotes osteogenesis and lymphopoiesis.
Cell Metab, 2022/08/02;34(8):1168-1182.e6.
Peng H[1], Hu B[1], Xie LQ[1], Su T[1], Li CJ[1], Liu Y[1], Yang M[1], Xiao Y[1], Feng X[1], Zhou R[1], Guo Q[1], Zhou HY[1], Huang Y[1], Jiang TJ[1], Luo XH[2]
Affiliations
PMID: 35705079DOI: 10.1016/j.cmet.2022.05.009
Impact factor: 31.373
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
MeSH terms
Animals; Bone Marrow; Bone Marrow Cells; Cell Differentiation; Cells, Cultured; Lipolysis; Lymphopoiesis; Mesenchymal Stem Cells; Mice; Osteogenesis
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