A potential theragnostic regulatory axis for arthrofibrosis involving adiponectin (Adipoq) receptor 1 and 2 (adipor1 and adipor2), tgfβ1, and smooth muscle α-actin (acta2)

Banu Bayram, Aaron R. Owen, Amel Dudakovic, Louis Dagneaux, Travis W. Turner, Jacob W. Bettencourt, Afton K. Limberg, Meagan E. Tibbo, Mark E. Morrey, Joaquin Sanchez-Sotelo, Daniel J. Berry, Jean Pierre A. Kocher, Andre J van Wijnen, Matthew P. Abdel

Research output: Contribution to journalArticlepeer-review

Abstract

(1) Background: Arthrofibrosis is a common cause of patient debility and dissatisfaction after total knee arthroplasty (TKA). The diversity of molecular pathways involved in arthrofibrosis disease progression suggest that effective treatments for arthrofibrosis may require a multimodal approach to counter the complex cellular mechanisms that direct disease pathogenesis. In this study, we leveraged RNA-seq data to define genes that are suppressed in arthrofibrosis patients and identified adiponectin (ADIPOQ) as a potential candidate. We hypothesized that signaling pathways activated by ADIPOQ and the cognate receptors ADIPOR1 and ADIPOR2 may prevent fibrosis-related events that contribute to arthrofibrosis. (2) Methods: Therefore, ADIPOR1 and ADIPOR2 were analyzed in a TGFβ1 inducible cell model for human myofibroblastogenesis by both loss-and gain-of-function experiments. (3) Results: Treatment with AdipoRon, which is a small molecule agonist of ADIPOR1 and ADIPOR2, decreased expression of collagens (COL1A1, COL3A1, and COL6A1) and the myofibroblast marker smooth muscle α-actin (ACTA2) at both mRNA and protein levels in basal and TGFβ1-induced cells. (4) Conclusions: Thus, ADIPOR1 and ADIPOR2 represent potential drug targets that may attenuate the pathogenesis of arthrofibrosis by suppressing TGFβ-dependent induction of myofibroblasts. These findings also suggest that AdipoRon therapy may reduce the development of arthrofibrosis by mediating anti-fibrotic effects in joint capsular tissues.

Original languageEnglish (US)
Article number3690
Pages (from-to)1-15
Number of pages15
JournalJournal of Clinical Medicine
Volume9
Issue number11
DOIs
StatePublished - Nov 2020

Keywords

  • Arthrofibrosis
  • Stiffness
  • Total knee arthroplasty (TKA)

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint

Dive into the research topics of 'A potential theragnostic regulatory axis for arthrofibrosis involving adiponectin (Adipoq) receptor 1 and 2 (adipor1 and adipor2), tgfβ1, and smooth muscle α-actin (acta2)'. Together they form a unique fingerprint.

Cite this