Smad4 is required to inhibit osteoclastogenesis and maintain bone mass

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K11268
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: Keio University
• Principal Investigator: Iwasaki Ryotaro 慶應義塾大学, 医学部(信濃町), 講師(非常勤) (30365390)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 骨代謝 / Smad4 / TGFβ / 破骨細胞

Outline of Final Research Achievements

Bone homeostasis is maintained as a delicate balance between bone-resorption and bone-formation, which are coupled to maintain appropriate bone mass. A critical question is how bone-resorption is terminated to allow bone-formation to occur. Here, we show that TGFβs inhibit osteoclastogenesis and maintain bone-mass through Smad4 activity in osteoclasts. We found that latent-TGFβ1 was activated by osteoclasts to inhibit osteoclastogenesis. Osteoclast-specific Smad4 conditional knockout mice (Smad4-cKO) exhibited significantly reduced bone-mass and elevated osteoclast formation relative to controls.Administration of latent-TGFβ1-Fc to wild-type mice antagonized LPS-induced bone destruction in a model of activated osteoclast-mediated bone destruction. Thus, latent-TGFβ1-Fc could serve as a promising new therapeutic agent in bone diseases marked by excessive resorption.

Free Research Field

骨代謝