RRC ID 76873
著者 Nagai T, Sekimoto T, Kurogi S, Ohta T, Miyazaki S, Yamaguchi Y, Tajima T, Chosa E, Imasaka M, Yoshinobu K, Araki K, Araki M, Choijookhuu N, Sato K, Hishikawa Y, Funamoto T.
タイトル Tmem161a regulates bone formation and bone strength through the P38 MAPK pathway.
ジャーナル Sci Rep
Abstract Bone remodeling is an extraordinarily complex process involving a variety of factors, such as genetic, metabolic, and environmental components. Although genetic factors play a particularly important role, many have not been identified. In this study, we investigated the role of transmembrane 161a (Tmem161a) in bone structure and function using wild-type (WT) and Tmem161a-depleted (Tmem161aGT/GT) mice. Mice femurs were examined by histological, morphological, and bone strength analyses. Osteoblast differentiation and mineral deposition were examined in Tmem161a-overexpressed, -knockdown and -knockout MC3T3-e1 cells. In WT mice, Tmem161a was expressed in osteoblasts of femurs; however, it was depleted in Tmem161aGT/GT mice. Cortical bone mineral density, thickness, and bone strength were significantly increased in Tmem161aGT/GT mice femurs. In MC3T3-e1 cells, decreased expression of alkaline phosphatase (ALP) and Osterix were found in Tmem161a overexpression, and these findings were reversed in Tmem161a-knockdown or -knockout cells. Microarray and western blot analyses revealed upregulation of the P38 MAPK pathway in Tmem161a-knockout cells, which referred as stress-activated protein kinases. ALP and flow cytometry analyses revealed that Tmem161a-knockout cells were resistant to oxidative stress. In summary, Tmem161a is an important regulator of P38 MAPK signaling, and depletion of Tmem161a induces thicker and stronger bones in mice.
巻・号 13(1)
ページ 14639
公開日 2023-9-5
DOI 10.1038/s41598-023-41837-4
PII 10.1038/s41598-023-41837-4
PMID 37670024
PMC PMC10480474
MeSH Alkaline Phosphatase Animals Bone Density Coloring Agents Craniocerebral Trauma* Mice Osteoblasts Osteogenesis* Oxidative Stress
IF 3.998
リソース情報
ヒト・動物細胞 MC3T3-E1(RCB1126)