Bone phenotype in melanocortin 2 receptor-deficient mice

Considering that stress condition associated with osteoporosis, the hypothalamic-pituitary-adrenal (HPA) axis, which is essential for central stress response system, is implicated in regulating bone mass accrual. Melanocortin 2 receptor (MC2R), the receptor of adrenocorticotropic hormone is expressed in both adrenal gland cells and bone cells. To elucidate the role of HPA axis in bone metabolism, we assessed the skeletal phenotype of MC2R deficient mice (MC2R(−/−) mice). We first examined bone mineral density and cortical thickness of femur using dual x-ray absorptiometry and micro-computed tomography. We then conducted histomorphometric analysis to calculate the static and dynamic parameters of vertebrae in MC2R(−/−) mice. The levels of osteoblastic marker genes were examined by quantitative PCR in primary osteoblasts derived from MC2R(−/−) mice. Based on these observations, bone mineral density of femur in MC2R(−/−) mice was increasing relative to litter controls. Meanwhile, the thickness of cortical bone of femur in MC2R(−/−) mice was remarkably elevated. Moreover, serum osteocalcin level was drastically raised in MC2R(−/−) mice. However, bone histomorphometry revealed that static and dynamic parameters reflecting bone formation and resorption were unchanged in vertebrae of MC2R(−/−) mice compared to the control, indicating that MC2R function may be specific to appendicular bone than axis bone. Taken together, the HPA axis due to deletion of MC2R is involved in bone metabolism.