Functional analysis of lubricin as an signaling molecule in regulation and maintenance of the superficial zone of the joint

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K09428
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: The University of Tokyo
• Principal Investigator: Uehara Kosuke 東京大学, 医学部附属病院, 病院診療医(出向) (20599063)
• Co-Investigator(Kenkyū-buntansha): 齋藤 琢 東京大学, 医学部附属病院, 准教授 (30456107) ; 森崎 裕 東京大学, 医学部附属病院, 病院診療医(出向) (30508099)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: Prg4 / ルブリシン / Superficial zone (SFZ) / 軟骨

Outline of Final Research Achievements

It has been postulated that the PRG4 gene, which encodes lubricin, structurally protects the joint by allowing for lubricity on the joint surface. Patients with mutations in the PRG4 gene develop arthritis at an early age, and Prg4 knockout (Prg4-KO) mice also develop osteoarthritis from juvenile stage. In Prg4-KO mice, their cartilage were thickened and the superficial layer of articular cartilage tissue (superficial zone, hereinafter referred to as SFZ) disappeared at the early postnatal period compared with wild-type mice. The comparison of the gene expressions of SFZ cells between Prg4-KO and wild-type mice revealed that genes associated with immune system processes, inflammation, and extracellular matrix genes were distinct. It was shown that PRG4 contributed to articular cartilage maintenance via the NfkB-Mmp9-TGF-b pathway from the detail analysis of the SFZ cells.

Free Research Field

整形外科

Academic Significance and Societal Importance of the Research Achievements

運動器に関わるルブリシンの研究のほとんどは潤滑性の維持に焦点を当てたものであり、それ以外の働きに関する報告はわずかである。その上、ルブリシンの分子レベルでのメカニズムの解析もほとんど進んでおらず、軟骨細胞を制御するという観点での研究や、ルブリシンをドメイン別に機能を解析した研究はない。我々の研究は、ルブリシンをシグナル伝達分子としての役割を見出した、今までのルブリシン研究とは一線を画したものであり、本研究は軟骨治療の新たな扉を開くものと考えている。