A comprehensive proteomic analysis for the Identification of factors contributing to hyaline cartilage regeneration

2018 Fiscal Year Final Research Report

• Project/Area Number: 16H05455
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Tokai University
• Principal Investigator: SATO Masato 東海大学, 医学部, 教授 (10056335)
• Co-Investigator(Kenkyū-buntansha): 豊田 恵利子 東海大学, 医学部, 特定研究員 (90749269)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: タンパク質 / miRNA / マイクロアレイ解析 / 細胞シート

Outline of Final Research Achievements

To identify the mechanisms and anabolic factors that contribute to the hyaline cartilage regenerative properties of chondrocyte sheets, we performed a proteomic analysis (SOMAscan) of factors that vary in correlation with the cartilage regenerative properties of chondrocyte sheets fabricated under different culture conditions and identified 26 such factors. Through the analysis of the change in levels of gene expression and secreted factors of chondrocyte sheets with varying cartilage regenerative properties, regulators of Wnt signaling, regulators of inflammation, and growth factors were found to correlate with the cartilage regenerative properties. Furthermore, through the microarray analysis of exosomal miRNAs in culture supernatants, miRNAs that correlate with the cartilage regenerative properties were identified. Validation through RT-PCR revealed 4 such miRNAs.

Free Research Field

整形外科学

Academic Significance and Societal Importance of the Research Achievements

軟骨細胞シートは、損傷した軟骨からのプロテオグリカンの流出の阻止や、関節液中の軟骨分解因子からの軟骨の保護に働き、軟骨成長因子の持続的な供給や、軟骨下骨から誘導される骨髄由来幹細胞に対する軟骨分化促進イニシエーターとしての機能等を介して軟骨修復を促進していると考えられるが、これらの作用にかかわる因子やメカニズムについては不明な点も多い。
自然には修復しない関節軟骨の再生に有用な因子の一端を明らかにした本研究成果は、軟骨細胞シートが軟骨修復を促進するメカニズムの解明に繋がるものである。