Recent progress in understanding molecular mechanisms of cartilage degeneration during osteoarthritis

Ann N Y Acad Sci. 2011 Dec;1240:61-9. doi: 10.1111/j.1749-6632.2011.06258.x.


Osteoarthritis (OA) is a highly prevalent disease affecting more than 20% of American adults. Predispositions include joint injury, heredity, obesity, and aging. Biomechanical alterations are commonly involved. However, the molecular mechanisms of this disease are complex, and there is currently no effective disease-modifying treatment. The initiation and progression of OA subtypes is a complex process that at the molecular level probably involves many cell types, signaling pathways, and changes in extracellular matrix. Ex vivo studies with tissue derived from OA patients and in vivo studies with mutant mice have suggested that pathways involving receptor ligands such as TGF-β1, WNT3a, and Indian hedgehog; signaling molecules such as Smads, β-catenin, and HIF-2a; and peptidases such as MMP13 and ADAMTS4/5 are probably involved to some degree. This review focuses on molecular mechanisms of OA development related to recent findings.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adult
  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Cartilage / metabolism*
  • Cartilage / pathology
  • Extracellular Matrix / metabolism*
  • Extracellular Matrix / pathology
  • Hedgehog Proteins / genetics
  • Hedgehog Proteins / metabolism
  • Humans
  • Mice
  • Mice, Mutant Strains
  • Osteoarthritis / epidemiology
  • Osteoarthritis / genetics
  • Osteoarthritis / metabolism*
  • Prevalence
  • Signal Transduction*
  • Smad Proteins / genetics
  • Smad Proteins / metabolism
  • Transforming Growth Factor beta1 / genetics
  • Transforming Growth Factor beta1 / metabolism
  • United States / epidemiology
  • Wnt3A Protein / genetics
  • Wnt3A Protein / metabolism
  • beta Catenin / genetics
  • beta Catenin / metabolism


  • Basic Helix-Loop-Helix Transcription Factors
  • Hedgehog Proteins
  • IHH protein, human
  • Smad Proteins
  • TGFB1 protein, human
  • Tgfb1 protein, rat
  • Transforming Growth Factor beta1
  • WNT3A protein, human
  • Wnt3A Protein
  • Wnt3a protein, mouse
  • beta Catenin
  • ihh protein, mouse
  • endothelial PAS domain-containing protein 1