MAGED1 is a negative regulator of bone remodeling in mice.
Melanoma antigen family D1 (MAGED1), an important adaptor protein, has been shown to ubiquitously express and play critical roles in many aspects of cellular events and physiological functions. However, its role in bone remodeling remains unknown. We, therefore, analyzed the bone phenotype of Maged1-deficient mice. Maged1-deficient mice displayed a significant osteoporotic phenotype with a marked decrease in bone density and deterioration of trabecular architecture. Histomorphometric analysis demonstrated an increased mineral apposition rate as well as increased osteoclast number and surface in Maged1 knockout mice. At the cellular level, Maged1-deficient osteoblasts exhibited an increased proliferation rate and accelerated differentiation. MAGED1 deficiency also caused a promotion in osteoclastogenesis, and that was attributed to the cell autonomous acceleration of differentiation in osteoclasts and an increased receptor activator of NF-κB ligand/osteoprotegerin ratio, a major index of osteoclastogenesis, in osteoblasts. Thus, we identified MAGED1 as a novel regulator of osteoblastogenesis, osteoclastogenesis, and bone remodeling in a mouse model.
Jiangsu Key Laboratory for Molecular and Medical Biotechnology, and College of Life Sciences, Nanjing Normal University, Nanjing, China.
Mei
M
Liu
Jiangsu Key Laboratory for Molecular and Medical Biotechnology, and College of Life Sciences, Nanjing Normal University, Nanjing, China.
Lijuan
L
Xu
Jiangsu Key Laboratory for Molecular and Medical Biotechnology, and College of Life Sciences, Nanjing Normal University, Nanjing, China.
Xiao
X
Ma
School of Pathology and Laboratory Medicine, University of Western Australia, Perth, Western Australia, Australia.
Jiake
J
Xu
Jiangsu Key Laboratory for Molecular and Medical Biotechnology, and College of Life Sciences, Nanjing Normal University, Nanjing, China.
Jing
J
Wang
Jiangsu Key Laboratory for Molecular and Medical Biotechnology, and College of Life Sciences, Nanjing Normal University, Nanjing, China.
Mengmeng
M
Xian
Jiangsu Key Laboratory for Molecular and Medical Biotechnology, and College of Life Sciences, Nanjing Normal University, Nanjing, China.
Xiaotian
X
Zhou
Jiangsu Key Laboratory for Molecular and Medical Biotechnology, and College of Life Sciences, Nanjing Normal University, Nanjing, China.
Min
M
Wang
Department of Cardiology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Fang
F
Wang
Shanghai Key Laboratory of Orthopaedic Implants, Ninth People's Hospital, Shanghai, China.
An
A
Qin
Central Laboratory, People's 10th Hospital, Shanghai, China.
Qiuhui
Q
Pan
Jiangsu Key Laboratory for Molecular and Medical Biotechnology, and College of Life Sciences, Nanjing Normal University, Nanjing, China. Electronic address: wenchuanjun@njnu.edu.cn.
Chuanjun
C
Wen
D000818:Animals; D015519:Bone Density / Q000502:physiology; D016723:Bone Remodeling / Q000235:genetics / Q000502:physiology*; D001862:Bone Resorption / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D010006:Osteoblasts / Q000378:metabolism*; D010010:Osteoclasts / Q000378:metabolism*; D053245:RANK Ligand / Q000378:metabolism
C486541:Maged1 protein, mouse; D016328:NF-kappa B; D009363:Neoplasm Proteins; D053245:RANK Ligand