Ripmeester Ellen G J, Steijns Jessica S J J, Wijnands Karolina A P, Stassen Roderick H M J, Pitelka Vasek, Peeters Laura C W, Cremers Andy, Astryde Nzekui M S A, Chabronova Alzbeta, Surtel Don A M, Emans Pieter J, van den Akker Guus G H, van Rietbergen Bert, van Rhijn Lodewijk W, Caron Marjolein M J, Welting Tim J M
Laboratory for Experimental Orthopedics, Department of Orthopedic Surgery, Maastricht University, Maastricht, The Netherlands.
Department of Physiology and Pharmacology, University of Western Ontario, London, ON, Canada.
Cartilage. 2024 Mar 19:19476035241233659. doi: 10.1177/19476035241233659.
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.
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.
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.
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.
骨关节炎（OA）的特征是关节软骨侵蚀、病理性软骨下骨改变以及滑膜炎症和疼痛迹象。我们之前鉴定出p[63 - 82]，这是一种源自骨形态发生蛋白7（BMP7）的生物活性肽，在大鼠内侧半月板撕裂创伤后骨关节炎模型中可减轻软骨结构退变。本研究旨在评估p[63 - 82]在另一种骨关节炎临床前模型（前交叉韧带横断 - 部分内侧半月板切除术[前交叉韧带横断（ACLT） - pMMx]）中减轻软骨侵蚀的活性。在该模型中对p[63 - 82]的疾病修饰作用进行了5周和10周的随访。
骨骼成熟的雄性Lewis大鼠接受ACLT - pMMx手术。大鼠每周接受关节内注射生理盐水或500 ng p[63 - 82]。术后5周和10周，处死大鼠，使用微型计算机断层扫描（µCT）确定软骨下骨特征。在番红O/固绿染色后进行软骨退变的组织病理学评估和国际骨关节炎研究学会（OARSI）评分。通过失能测试和足迹分析测量疼痛相关行为。
术后5周和10周的组织病理学评估显示软骨退变减轻，OARSI评分显著降低，而与生理盐水处理的大鼠相比，p[63 - 82]处理的大鼠软骨下骨特征无显著变化。与生理盐水处理的大鼠相比，术后5周时，p[63 - 82]组中ACLT - pMMx诱导的静态负重能力失衡得到显著改善。p[63 - 82]处理的大鼠的足迹分析评分在术后10周显示有所改善。
在大鼠ACLT - pMMx创伤后骨关节炎模型中，每周关节内注射p[63 - 82]可减少软骨退变，并在随访期间改善静态负重能力的功能。
