Loss-of-function of SHARPIN causes an osteopenic phenotype in mice.
SHARPIN is a novel protein thought to interact with SHANK family and is widely expressed in multiple tissues/cells, including osteoblasts and osteoclasts. Loss-of-function of Sharpin develops the chronic proliferative dermatitis mutation (CPDM) in mice as well as a severe inflammation in other organs. The actual function of SHARPIN is poorly understood. Our aim was to determine the functional roles of SHARPIN in bone metabolism by using CPDM mice. The skeletal phenotypes were determined by peripheral quantitative computed tomography, micro-computed tomography, and quantitative real-time RT-PCR, the cellular functions of osteoblasts and osteoclasts were investigated by ex vivo cell culture. Compared to wild-type controls, CPDM mice demonstrated significantly lower total and cortical bone mineral content and bone mineral density, trabecular and cortical bone volume, and trabecular number. The mRNA expression of Runx2, osterix, type I collagen, and osteocalcin was significantly lower in the bone from CPDM mice. Osteoclasts and osteoblasts from CPDM mice were functionally defective. Our result suggests that SHARPIN plays important regulating roles in bone metabolism. These functional roles may either come from systemic chronic inflammatory or directly signaling pathway within bone cells.
Laboratory of Endocrinology and Metabolism, West China Hospital, Sichuan University, No. 37, Guoxue Xiang, Chengdu, People's Republic of China.
Tian
T
Xia
Yanhua
Y
Liang
Junrong
J
Ma
Mi
M
Li
Meng
M
Gong
Xijie
X
Yu
D000818:Animals; D015519:Bone Density / Q000235:genetics; D001851:Bone Diseases, Metabolic / Q000235:genetics / Q000276:immunology / Q000503:physiopathology*; D001842:Bone and Bones / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D002113:Calcification, Physiologic; D002478:Cells, Cultured; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D016368:Frameshift Mutation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D010006:Osteoblasts / Q000378:metabolism / Q000648:ultrastructure; D015675:Osteocalcin / Q000235:genetics / Q000378:metabolism; D010010:Osteoclasts / Q000378:metabolism / Q000648:ultrastructure; D012333:RNA, Messenger / Q000378:metabolism; D000076182:Sp7 Transcription Factor; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D024042:Collagen Type I; D050659:Core Binding Factor Alpha 1 Subunit; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C493716:Runx2 protein, mouse; D000076182:Sp7 Transcription Factor; C479466:Sp7 protein, mouse; D014157:Transcription Factors; C425287:sharpin; D015675:Osteocalcin