iScience (Jul 2023)

Ablation of collagen XII disturbs joint extracellular matrix organization and causes patellar subluxation

  • Mengjie Zhu,
  • Fabian Metzen,
  • Mark Hopkinson,
  • Janina Betz,
  • Juliane Heilig,
  • Jassi Sodhi,
  • Thomas Imhof,
  • Anja Niehoff,
  • David E. Birk,
  • Yayoi Izu,
  • Marcus Krüger,
  • Andrew A. Pitsillides,
  • Janine Altmüller,
  • Gerjo J.V.M. van Osch,
  • Volker Straub,
  • Gudrun Schreiber,
  • Mats Paulsson,
  • Manuel Koch,
  • Bent Brachvogel

Journal volume & issue
Vol. 26, no. 7
p. 107225

Abstract

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Summary: Collagen XII, belonging to the fibril-associated collagens, is a homotrimeric secreted extracellular matrix (ECM) protein encoded by the COL12A1 gene. Mutations in the human COL12A1 gene cause an Ehlers-Danlos/myopathy overlap syndrome leading to skeletal abnormalities and muscle weakness. Here, we studied the role of collagen XII in joint pathophysiology by analyzing collagen XII deficient mice and human patients. We found that collagen XII is widely expressed across multiple connective tissue of the developing joint. Lack of collagen XII in mice destabilizes tendons and the femoral trochlear groove to induce patellar subluxation in the patellofemoral joint. These changes are associated with an ECM damage response in tendon and secondary quadriceps muscle degeneration. Moreover, patellar subluxation was also identified as a clinical feature of human patients with collagen XII deficiency. The results provide an explanation for joint hyperlaxity in mice and human patients with collagen XII deficiency.

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