Mats1과 Mats2 이중결손 유전자 돌연변이에 의한 골감소증 기전에 대한 연구
Osteoporotic bone phenotype in Mats1/2 double-mutant mice
오주환, 최윤정, 유미현, 배문경, 김형준,
소속 상세정보
오주환 ( Oh Ju-Hwan ) - 부산대학교 치의학전문대학원 구강생리학교실
최윤정 ( Choi Yun-Jeong ) - 부산대학교 치의학전문대학원 구강생리학교실
유미현 ( Ryu Mi-Heon ) - 부산대학교 치의학전문대학원 구강병리학교실
배문경 ( Bae Moon-Kyung ) - 부산대학교 치의학전문대학원 구강생리학교실
김형준 ( Kim Hyung-Joon ) - 부산대학교 치의학전문대학원 구강생리학교실
Abstract
The Hippo pathway was originally discovered in Drosophila by genetic screening and it has been shown to be conserved in various organisms including human. Until now, the essential roles of Hippo pathway in regulating cell proliferation, apoptosis, tumorigenesis, and organ size control is extensively studied. Currently, Mats1/2 (Mob1a/1b), one of the important components in Hippo pathway, mutant mice were generated which has abnormal phenotype such as resistance to apoptosis and spontaneous tumorigenesis. Of note, Mats1/2 mutant mice also showed dental malocclusion. Therefore, in this study, we have evaluated the bone phenotype of Mats1/2 mutant mice. Although the mRNA expressions of Mats1 or Mats2 were observed in both osteoclastogenesis and osteoblastogenesis, the increase of Mats1 level was most prominent during osteoblastogenesis. The RANKL-induced osteoclast differentiation from bone marrow-derived macrophages (BMMs) was unaltered upon Mats1/2 mutation; however, the osteoblast differentiation using calvarial pre-osteoblasts was significantly reduced in Mats1/2 mutant mice compare to that of wild type mice. In accordance with in vitro results, Mats1/2 mutant mice showed decreased bone volume as well as increased trabecular separation in μCT analyses. These results may provide novel prospect of the probable linkage between Hippo pathway and bone homeostasis.
키워드
Hippo pathway; osteoclast; osteoblast; Runx2
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