Mechanisms of reducing joint stiffness by blocking collagen fibrillogenesis in a rabbit model of posttraumatic arthrofibrosis

PLoS One. 2021 Sep 7;16(9):e0257147. doi: 10.1371/journal.pone.0257147. eCollection 2021.

Abstract

Posttraumatic fibrotic scarring is a significant medical problem that alters the proper functioning of injured tissues. Current methods to reduce posttraumatic fibrosis rely on anti-inflammatory and anti-proliferative agents with broad intracellular targets. As a result, their use is not fully effective and may cause unwanted side effects. Our group previously demonstrated that extracellular collagen fibrillogenesis is a valid and specific target to reduce collagen-rich scar buildup. Our previous studies showed that a rationally designed antibody that binds the C-terminal telopeptide of the α2(I) chain involved in the aggregation of collagen molecules limits fibril assembly in vitro and reduces scar formation in vivo. Here, we have utilized a clinically relevant arthrofibrosis model to study the broad mechanisms of the anti-scarring activity of this antibody. Moreover, we analyzed the effects of targeting collagen fibril formation on the quality of healed joint tissues, including the posterior capsule, patellar tendon, and subchondral bone. Our results show that blocking collagen fibrillogenesis not only reduces collagen content in the scar, but also accelerates the remodeling of healing tissues and changes the collagen fibrils' cross-linking. In total, this study demonstrated that targeting collagen fibrillogenesis to limit arthrofibrosis affects neither the quality of healing of the joint tissues nor disturbs vital tissues and organs.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antibodies / metabolism
  • Biomarkers / blood
  • CHO Cells
  • Calcification, Physiologic
  • Cricetulus
  • Disease Models, Animal
  • Female
  • Fibrillar Collagens / metabolism*
  • Fibrosis
  • Joint Capsule / metabolism
  • Joint Capsule / pathology
  • Joint Capsule / physiopathology
  • Joint Diseases / pathology*
  • Joint Diseases / physiopathology*
  • Joints / physiopathology*
  • Male
  • Rabbits
  • Spectroscopy, Fourier Transform Infrared
  • Time Factors

Substances

  • Antibodies
  • Biomarkers
  • Fibrillar Collagens

Grants and funding

Grants from the Department of Defense supported this research: W81XWH-18-1-0554 awarded to AF.