Poster Presentation Annual Meetings of the Endocrine Society of Australia and Society for Reproductive Biology and Australia and New Zealand Bone and Mineral Society 2016

Mitochondrial respiratory supercomplex assembly-promoting factor COX7RP regulates bone metabolism in mice (#272)

Kazuhiro Ikeda 1 , Sachiko Shiba 1 , Kuniko Horie-Inoue 1 , Satoshi Inoue 1 2
  1. Saitama Medical University, Hidaka, SAITAMA, Japan
  2. Department of Functional Biogerontology, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan

Bone is a dynamic tissue whose mass is regulated by the balance between bone resorption by osteoclasts and bone formation by osteoblasts. Unbalanced bone turnover causes metabolic bone diseases including osteoporosis. Mitochondria are cytoplasmic organelles which take part in a variety of cellular metabolic functions. Therefore, mitochondrial function in bone metabolism has attracted much attention; however, the mechanism is not fully understood. We originally identified COX7RP as an estrogen-responsive gene, and recently found that COX7RP stimulates formation of mitochondrial respiratory supercomplexes leading to efficient ATP production (Nat Commun 4, 2147, 2013). In the present study, we investigated the bone phenotypes of Cox7rp knockout male mice. Dual-energy X-ray absorptiometry (DEXA) analysis revealed that the knockout mice have a decreased bone mineral density (BMD) of the femur compared with wild type mice. Bone morphometric analysis showed that bone volume is decreased, whereas the parameters such as bone formation rate, osteoblast number, and osteoclast number are higher in the tibia of knockout mice than that of wild type mice. Bone strength test revealed that the maximum peak load is significantly smaller in the knockout mice than wild type mice. We also cultured osteoblastic and osteoclastic cells derived from the knockout mice, and explored the gene expression. These results indicated that the Cox7rp knockout mice exhibit osteopenia phenotype with high bone-turnover. Taken together, mitochondrial respiratory supercomplex assembly-promoting factor COX7RP would contribute to the regulation of the bone metabolism in vivo.