Bone phenotype in melanocortin 2 receptor-deficient mice
Tsuyoshi Sato,
Takanori Iwata,
Michihiko Usui,
Shoichiro Kokabu,
Yasutaka Sugamori,
Yuki Takaku,
Takashi Kobayashi,
Ko Ito,
Masahito Matsumoto,
Shu Takeda,
Ren Xu,
Dai Chida
Affiliations
Tsuyoshi Sato
Department of Oral and Maxillofacial Surgery, Saitama Medical University, Saitama, Japan; Corresponding author at: Department of Oral and Maxillofacial Surgery, Saitama Medical University, 38 Moro-hongou, Moroyama-machi, Iruma-gun, Saitama 350-0495, Japan.
Takanori Iwata
Department of Periodontology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan
Michihiko Usui
Division of Periodontology, Department of Cardiology and Periodontology, Kyushu Dental University, Fukuoka, Japan
Shoichiro Kokabu
Division of Molecular Signaling and Biochemistry, Department of Health Promotion, Kyushu Dental University, Kokurakita-ku, Kitakyushu, Fukuoka, Japan
Yasutaka Sugamori
Department of Oral and Maxillofacial Surgery, Saitama Medical University, Saitama, Japan
Yuki Takaku
Department of Oral and Maxillofacial Surgery, Saitama Medical University, Saitama, Japan
Takashi Kobayashi
Department of Oral and Maxillofacial Surgery, Saitama Medical University, Saitama, Japan
Ko Ito
Department of Oral and Maxillofacial Surgery, Saitama Medical University, Saitama, Japan
Masahito Matsumoto
Department of Biofunction Research, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Tokyo, Japan
Shu Takeda
Department of Endocrinology and Metabolism, Toranomon Hospital, Tokyo, Japan
Ren Xu
State Key Laboratory of Cellular Stress Biology, School of Medicine, Xiamen University, Xiamen, China
Dai Chida
Department of Oral and Maxillofacial Surgery, Saitama Medical University, Saitama, Japan; SanBio, Tokyo, Japan
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.
