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Software-Assisted Quantitative Measurement of Osteoarthritic Subchondral Bone Thickness
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ADRM1/RPN13 attenuates cartilage extracellular matrix degradation via enhancing UCH37-mediated ALK5 deubiquitination

Meisong Zhu1, Zhiyou Cao1, Fengbo Mo1

  • 1Department of Orthopedics, The First Affiliated Hospital of Nanchang University, Artificial Joints Engineering and Technology Research Center of Jiangxi Province, Nanchang, Jiangxi province 330006, China.

International Journal of Biological Macromolecules
|July 5, 2023
PubMed

Insights

Adhesion-regulating molecule 1 (ADRM1) protects against osteoarthritis (OA) by maintaining cartilage health. Lower ADRM1 levels worsen OA, while boosting it offers a potential therapeutic strategy for this common joint disorder.

Area of Science:

  • Biomedical research
  • Orthopedics
  • Molecular biology

Background:

  • Osteoarthritis (OA) is a prevalent age-related joint disease with unclear pathological mechanisms and limited therapeutic options.
  • Adhesion-regulating molecule 1 (ADRM1) is implicated in OA progression, but its precise role and mechanism remain elusive.

Purpose of the Study:

  • To elucidate the role and molecular mechanism of ADRM1 in osteoarthritis.
  • To investigate ADRM1's potential as a therapeutic target for OA.

Main Methods:

  • Analysis of ADRM1 expression in human and mouse OA cartilage and chondrocytes.
  • Utilizing global ADRM1 knockout mice and ADRM1 inhibitor (RA190) in a destabilization of the medial meniscus (DMM) OA model.
  • Investigating molecular interactions between ADRM1, ubiquitin carboxy-terminal hydrolase 37 (UCH37), and activin receptor-like kinase 5 (ALK5).

Main Results:

  • ADRM1 expression was decreased in OA cartilage and chondrocytes.
  • Loss of ADRM1 accelerated cartilage degeneration in DMM-induced OA, while ADRM1 overexpression conferred protection.
  • ADRM1 was found to upregulate UCH37, enhancing its deubiquitination activity and stabilizing ALK5, thereby maintaining extracellular matrix (ECM) homeostasis.

Conclusions:

  • ADRM1 attenuates cartilage degeneration in OA by promoting UCH37-mediated deubiquitination and stabilization of ALK5.
  • ADRM1 plays a protective role in maintaining articular cartilage homeostasis.
  • Overexpression of ADRM1 presents a promising therapeutic strategy for osteoarthritis.
Keywords:
ADRM1ALK5ChondrocyteOsteoarthritisUCH37

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