A study of increase bone volume using transgenic mice with osteoblasts that express proliferation and anti-apoptotic factors

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K10482
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Nagasaki University
• Principal Investigator: MORIISHI Takeshi 長崎大学, 医歯薬学総合研究科(歯学系), 助教 (20380983)
• Co-Investigator(Kenkyū-buntansha): 福田 理香 活水女子大学, 健康生活学部, 教授 (30312838)
• Co-Investigator(Renkei-kenkyūsha): KOMORI Toshihisa 長崎大学, 医歯薬学総合研究科(歯学系), 教授 (00252677) ; MIYAZAKI Toshihiro 長崎大学, 医歯薬学総合研究科(歯学系), 准教授 (10174161)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: アポトーシス / 骨芽細胞 / BCLXL / 過剰発現マウス / 骨形成 / 骨粗鬆症

Outline of Final Research Achievements

Osteoblast apoptosis plays an important role in bone development and maintenance. It is estimated that 60% to 80% of osteoblasts that originally assembled at the resorption pit die by apoptosis. We generated BCLXL (BCL2L1) transgenic mice using the 2.3 kb Col1a1 promoter to investigate BCLXL functions in bone development and maintenance. BrdU-positive osteoblastic cell numbers were increased, TUNEL-positive osteoblastic cell numbers were reduced in BCLXL transgenic mice. The three-point bending test indicated that femurs were stronger in BCLXL transgenic mice than in wild-type mice. Increased trabecular and cortical bone volumes were maintained during aging in male and female mice. These results indicate that BCLXL overexpression in osteoblasts increased the trabecular and cortical bone volumes with normal structures and maintained them majorly by preventing osteoblast apoptosis, implicating BCLXL as a therapeutic target of osteoporosis.

Free Research Field

骨・軟骨代謝学