The BMP7-Derived Peptide p[63-82] Reduces Cartilage Degeneration in the Rat ACLT-pMMx Model for Posttraumatic Osteoarthritis.

Autor: Ripmeester EGJ; Laboratory for Experimental Orthopedics, Department of Orthopedic Surgery, Maastricht University, Maastricht, The Netherlands., Steijns JSJJ; Laboratory for Experimental Orthopedics, Department of Orthopedic Surgery, Maastricht University, Maastricht, The Netherlands., Wijnands KAP; Laboratory for Experimental Orthopedics, Department of Orthopedic Surgery, Maastricht University, Maastricht, The Netherlands., Stassen RHMJ; Laboratory for Experimental Orthopedics, Department of Orthopedic Surgery, Maastricht University, Maastricht, The Netherlands., Pitelka V; Department of Physiology and Pharmacology, University of Western Ontario, London, ON, Canada., Peeters LCW; Laboratory for Experimental Orthopedics, Department of Orthopedic Surgery, Maastricht University, Maastricht, The Netherlands., Cremers A; Laboratory for Experimental Orthopedics, Department of Orthopedic Surgery, Maastricht University, Maastricht, The Netherlands., Astryde NMSA; Laboratory for Experimental Orthopedics, Department of Orthopedic Surgery, Maastricht University, Maastricht, The Netherlands., Chabronova A; Laboratory for Experimental Orthopedics, Department of Orthopedic Surgery, Maastricht University, Maastricht, The Netherlands., Surtel DAM; Laboratory for Experimental Orthopedics, Department of Orthopedic Surgery, Maastricht University, Maastricht, The Netherlands., Emans PJ; Laboratory for Experimental Orthopedics, Department of Orthopedic Surgery, Maastricht University, Maastricht, The Netherlands.; Laboratory for Experimental Orthopedics, Department of Orthopedic Surgery, Maastricht University Medical Center, Maastricht, The Netherlands., van den Akker GGH; Laboratory for Experimental Orthopedics, Department of Orthopedic Surgery, Maastricht University, Maastricht, The Netherlands., van Rietbergen B; Department of Biomedical Engineering, Orthopaedic Biomechanics, Eindhoven University of Technology, Eindhoven, The Netherlands., van Rhijn LW; Laboratory for Experimental Orthopedics, Department of Orthopedic Surgery, Maastricht University, Maastricht, The Netherlands.; Laboratory for Experimental Orthopedics, Department of Orthopedic Surgery, Maastricht University Medical Center, Maastricht, The Netherlands., Caron MMJ; Laboratory for Experimental Orthopedics, Department of Orthopedic Surgery, Maastricht University, Maastricht, The Netherlands.; Laboratory for Experimental Orthopedics, Department of Orthopedic Surgery, Maastricht University Medical Center, Maastricht, The Netherlands., Welting TJM; Laboratory for Experimental Orthopedics, Department of Orthopedic Surgery, Maastricht University, Maastricht, The Netherlands.; Laboratory for Experimental Orthopedics, Department of Orthopedic Surgery, Maastricht University Medical Center, Maastricht, The Netherlands.
Jazyk: angličtina
Zdroj: Cartilage [Cartilage] 2024 Mar 19, pp. 19476035241233659. Date of Electronic Publication: 2024 Mar 19.
DOI: 10.1177/19476035241233659
Abstrakt: Objective: Osteoarthritis (OA) is characterized by articular cartilage erosion, pathological subchondral bone changes, and signs of synovial inflammation and pain. We previously identified p[63-82], a bone morphogenetic protein 7 (BMP7)-derived bioactive peptide that attenuates structural cartilage degeneration in the rat medial meniscal tear-model for posttraumatic OA. This study aimed to evaluate the cartilage erosion-attenuating activity of p[63-82] in a different preclinical model for OA (anterior cruciate ligament transection-partial medial meniscectomy [anterior cruciate ligament transection (ACLT)-pMMx]). The disease-modifying action of the p[63-82] was followed-up in this model for 5 and 10 weeks.
Design: Skeletally mature male Lewis rats underwent ACLT-pMMx surgery. Rats received weekly intra-articular injections with either saline or 500 ng p[63-82]. Five and 10 weeks postsurgery, rats were sacrificed, and subchondral bone characteristics were determined using microcomputed tomography (µCT). Histopathological evaluation of cartilage degradation and Osteoarthritis Research Society International (OARSI)-scoring was performed following Safranin-O/Fast Green staining. Pain-related behavior was measured by incapacitance testing and footprint analysis.
Results: Histopathological evaluation at 5 and 10 weeks postsurgery showed reduced cartilage degeneration and a significantly reduced OARSI score, whereas no significant changes in subchondral bone characteristics were found in the p[63-82]-treated rats compared to the saline-treated rats. ACLT-pMMx-induced imbalance of static weightbearing capacity in the p[63-82] group was significantly improved compared to the saline-treated rats at weeks 5 postsurgery. Footprint analysis scores in the p[63-82]-treated rats demonstrated improvement at week 10 postsurgery.
Conclusions: Weekly intra-articular injections of p[63-82] in the rat ACLT-pMMx posttraumatic OA model resulted in reduced degenerative cartilage changes and induced functional improvement in static weightbearing capacity during follow-up.
Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: MC and TW are listed as the inventor on filed patents: WO2017178251 and WO2017178253. TW, PE, and LR have shares in Chondropeptix BV.
Databáze: MEDLINE