1. Skeletal muscle mitoribosomal defects are linked to low bone mass caused by bone marrow inflammation in male mice
- Author
-
Jingwen Tian, Hyo Kyun Chung, Ji Sun Moon, Ha Thi Nga, Ho Yeop Lee, Jung Tae Kim, Joon Young Chang, Seul Gi Kang, Dongryeol Ryu, Xiangguo Che, Je‐Yong Choi, Masayuki Tsukasaki, Takayoshi Sasako, Sang‐Hee Lee, Minho Shong, and Hyon‐Seung Yi
- Subjects
Mitochondria ,Inflammation ,Bone marrow ,Bone loss ,Diseases of the musculoskeletal system ,RC925-935 ,Human anatomy ,QM1-695 - Abstract
Abstract Background Mitochondrial oxidative phosphorylation (OxPhos) is a critical regulator of skeletal muscle mass and function. Although muscle atrophy due to mitochondrial dysfunction is closely associated with bone loss, the biological characteristics of the relationship between muscle and bone remain obscure. We showed that muscle atrophy caused by skeletal muscle‐specific CR6‐interacting factor 1 knockout (MKO) modulates the bone marrow (BM) inflammatory response, leading to low bone mass. Methods MKO mice with lower muscle OxPhos were fed a normal chow or high‐fat diet and then evaluated for muscle mass and function, and bone mineral density. Immunophenotyping of BM immune cells was also performed. BM transcriptomic analysis was used to identify key factors regulating bone mass in MKO mice. To determine the effects of BM‐derived CXCL12 (C–X–C motif chemokine ligand 12) on regulation of bone homeostasis, a variety of BM niche‐resident cells were treated with recombinant CXCL12. Vastus lateralis muscle and BM immune cell samples from 14 patients with hip fracture were investigated to examine the association between muscle function and BM inflammation. Results MKO mice exhibited significant reductions in both muscle mass and expression of OxPhos subunits but increased transcription of mitochondrial stress response‐related genes in the extensor digitorum longus (P
- Published
- 2022
- Full Text
- View/download PDF