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Protocadherin-7 contributes to maintenance of bone homeostasis through regulation of osteoclast multinucleation

BMB Reports 2020년 53권 9호 p.472 ~ 477
김현수, Takegahara Noriko, Walsh Matthew C., Ueda Jun, Fujihara Yoshitaka, Ikawa Masahito, 최용원,
소속 상세정보
김현수 ( Kim Hyun-Soo ) - University of Pennsylvania Perelman School of Medicine Department of Pathology and Laboratory Medicine
 ( Takegahara Noriko ) - University of Pennsylvania Perelman School of Medicine Department of Pathology and Laboratory Medicine
 ( Walsh Matthew C. ) - University of Pennsylvania Perelman School of Medicine Department of Pathology and Laboratory Medicine
 ( Ueda Jun ) - Osaka University Research Institute for Microbial Diseases
 ( Fujihara Yoshitaka ) - Osaka University Research Institute for Microbial Diseases
 ( Ikawa Masahito ) - Osaka University Research Institute for Microbial Diseases
최용원 ( Choi Yong-Won ) - University of Pennsylvania Perelman School of Medicine Department of Pathology and Laboratory Medicine

Abstract


Osteoclasts are hematopoietic-derived cells that resorb bone. They are required to maintain proper bone homeostasis and skeletal strength. Although osteoclast differentiation depends on receptor activator of NF-κB ligand (RANKL) stimulation, additional molecules further contribute to osteoclast maturation. Here, we demonstrate that protocadherin-7 (Pcdh7) regulates formation of multinucleated osteoclasts and contributes to maintenance of bone homeostasis. We found that Pcdh7 expression is induced by RANKL stimulation, and that RNAi-mediated knockdown of Pcdh7 resulted in impaired formation of osteoclasts. We generated Pcdh7-deficient mice and found increased bone mass due to decreased bone resorption but without any defect in bone formation. Using an in vitro culture system, it was revealed that formation of multinucleated osteoclasts is impaired in Pcdh7-deficient cultures, while no apparent defects were observed in differentiation and function of Pcdh7-deficient osteoblasts. Taken together, these results reveal an osteoclast cell-intrinsic role for Pcdh7 in maintaining bone homeostasis.

키워드

Bone homeostasis; Maturation; Multinucleation; Osteoclast; Pcdh7

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