2022 Fiscal Year Final Research Report
Subchondral bone loss in early knee osteoarthritis: osteocyte apoptosis and RANKL expression
| Project/Area Number |
20K09443
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 56020:Orthopedics-related
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| Research Institution | Kindai University |
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Principal Investigator |
AKAGI Masao 近畿大学, 医学部, 教授 (00273441)
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| Co-Investigator(Kenkyū-buntansha) |
橋本 和彦 近畿大学, 医学部, 講師 (10635569)
墳本 一郎 近畿大学, 医学部, 講師 (20770051)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | 早期変形性膝関節症 / 軟骨下骨 / 骨量減少 / 異常骨リモデリング / 骨細胞死 / RANKL / 局所レニン・アンギオテンシン系 / 閉経後骨粗鬆症 |
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| Outline of Final Research Achievements |
Knee OA was produced by the DMM(destabilization of medial meniscus)surgery for 40-week-old wild type mice and Tsukuba hypertensive mice(THM)with high tourn-over osteoporosis. Changes in bone parameters and shape in the medial tibial subchondral bone(SB)were observed by μCT. Numbers of osteocytes,TRAP positive and RANKL positive cells in the SB were counted histologically.BV/TV and BMD decreased with time after operation, and significant differences were noted after 4 and 8 weeks, respectively. 12 weeks after the DMM surgery, however, an increase in BV/TV with a decrease in BMD was noted. Height of the medial tibial SB decreased with time and a significant decrease was noted after 12 weeks. Number of osteocytes in the SB decreased with time and a significant decrease was noted after 4 weeks. TRAP positive and RANKL positive cells increased with time and significant increases were noted after 2 weeks, respectively. In THM, all these changes above mentioned was enhanced significantly.
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| Free Research Field |
変形性膝関節症、局所レニン・アンギオテンシン系、人工関節置換術
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| Academic Significance and Societal Importance of the Research Achievements |
早期OAにおいては、軟骨下骨の骨吸収が生じ、その後に軟骨下の骨異常リモデリングと骨形態変化が生じることが示された。また、この骨吸収には、軟骨下骨におけるmicrocrackやmicrofractureに伴う骨細胞死と周囲の生存骨細胞におけるRANKL発現と破骨細胞活性化が関与することが示唆された。
以上より、膝OAの予防や発症抑制には発症前後の軟骨下骨の健全性の維持が極めて重要であり、これを目的とした生活指導、食事療法、運動療法や薬物療法の体系化が必要と思われる。また、THMにおいて上記の機序が著しく加速されることより、閉経後骨粗鬆症予防は女性の膝OAに対する重要な予防戦略となる可能性がある。
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