FAM210A is a novel determinant of bone and muscle structure and strength.

Abstract

Osteoporosis and sarcopenia are common comorbid diseases, yet their shared mechanisms are largely unknown. We found that genetic variation near <i>FAM210A</i> was associated, through large genome-wide association studies, with fracture, bone mineral density (BMD), and appendicular and whole body lean mass, in humans. In mice, <i>Fam210a</i> was expressed in muscle mitochondria and cytoplasm, as well as in heart and brain, but not in bone. Grip strength and limb lean mass were reduced in tamoxifen-inducible <i>Fam210a</i> homozygous global knockout mice (<i>TFam210a</i>^<i>-/-</i> ), and in tamoxifen-inducible <i>Fam210</i> skeletal muscle cell-specific knockout mice (<i>TFam210aMus</i>^<i>-/-</i> ). Decreased BMD, bone biomechanical strength, and bone formation, and elevated osteoclast activity with microarchitectural deterioration of trabecular and cortical bones, were observed in <i>TFam210a</i>^<i>-/-</i> mice. BMD of male <i>TFam210aMus</i>^<i>-/-</i> mice was also reduced, and osteoclast numbers and surface in <i>TFam210aMus</i>^<i>-/-</i> mice increased. Microarray analysis of muscle cells from <i>TFam210aMus</i>^<i>-/-</i> mice identified candidate musculoskeletal modulators. <i>FAM210A</i>, a novel gene, therefore has a crucial role in regulating bone structure and function, and may impact osteoporosis through a biological pathway involving muscle as well as through other mechanisms.