Activity, Motor Control & Coordination
Pain - Thermal Allodynia / Hyperalgesia
Pain - Spontaneous Pain - Postural Deficit
Pain - Mechanical Allodynia / Hyperalgesia
Anxiety & Depression Disorder
Learning/Memory - Attention - Addiction
Physiology & Respiratory Research
Metabolism - Food & Drink Intake
Pain
Metabolism
Motor control
Neurodegeneration
Cross-disciplinary subjects
Muscular system
General activity
Mood Disorders
Other disorders
Joints
Central Nervous System (CNS)
Sensory system
Authors
K Tanaka, Y Xue, L Nguyen-Yamamoto, JA Morris, I Kanazawa, T Sugimoto, SS Wing, JB Richards, D Goltzman
Lab
McGill University, Montreal, QC, Canada
Journal
PNAS
Abstract
Osteoporosis and sarcopenia are common comorbid diseases, yet their shared mechanisms are largely unknown. We found that genetic variation near FAM210A 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, Fam210a 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 Fam210a homozygous global knockout mice (TFam210a_/_), and in tamoxifen-inducible Fam210 skeletal muscle cell-specific knockout mice (TFam210aMus_/_). Decreased BMD, bone biomechanical strength, and bone formation, and elevated osteoclast activity with microarchitectural deterioration of trabecular and cortical bones, were observed in TFam210a_/_ mice. BMD of male TFam210aMus_/_ mice was also reduced, and osteoclast numbers and surface in TFam210aMus_/_ mice increased. Microarray analysis of muscle cells from TFam210aMus_/_ mice identified candidate musculoskeletal modulators. FAM210A, 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.
BIOSEB Instruments Used:
Grip strength test (BIO-GS3)
