Efficacy of ADIPOR1 and ADIPOR2 peptide‐agonist AdipoRon in preventing contracture in a rabbit model of arthrofibrosis

• Published in: Journal of orthopaedic research 2024-09, Vol.42 (9), p.1916-1922
• Main Authors: Salmons, Harold I., Carstens, Mason F., Limberg, Afton K., Bettencourt, Jacob W., Payne, Ashley N., Karczewski, Daniel C., Ryan, Zachary T., Morrey, Mark E., Sanchez‐Sotelo, Joaquin, Berry, Daniel J., Dudakovic, Amel, Abdel, Matthew P.
• Format: Article
• Language: English
• Subjects: adiponectin; Animals; Contracture - drug therapy; Contracture - etiology; Contracture - prevention & control; Disease Models, Animal; Female; Fibrosis; Piperidines - pharmacology; Piperidines - therapeutic use; prevention; Rabbits; Receptors, Adiponectin - agonists; stiffness; TGFβ1; total knee arthroplasty (TKA)
• ISSN: 0736-0266; 1554-527X; 1554-527X
• DOI: 10.1002/jor.25853

AdipoRon is an adiponectin receptor 1, 2 (ADIPOR1 and ADIPOR2) agonist with potential antifibrotic effects. Whether AdipoRon can mitigate joint stiffness in a rabbit model of arthrofibrosis is unknown. We examined the efficacy of intravenous (IV) AdipoRon at mitigating contracture in a rabbit model of knee arthrofibrosis. Fifty‐six female New Zealand White rabbits were divided into three dosing groups: vehicle (dimethyl sulfoxide, DMSO), 2.5 mg/kg AdipoRon, and 5 mg/kg AdipoRon. AdipoRon, in DMSO, was administered IV preoperatively and for 5 days postoperatively (30 rabbits, Aim 1). AdipoRon was again dosed similarly after Kirschner wire (K‐wire) removal at 8 weeks (26 rabbits; Aim 2). The primary outcome of joint passive extension angle (PEA,°) was measured at 8, 10, 12, 16, and 24 weeks following index surgery. At 24 weeks, rabbits were euthanized and limbs were harvested to measure posterior capsular stiffness (N cm/°). In Aim 1, the 5 mg/kg treated rabbits had a significant increase in PEA when compared to controls at 16‐week (p