Macfadyen Mhairi A, Daniel Zoe, Kelly Sara, Parr Tim, Brameld John M, Murton Andrew J, Jones Simon W
MRC-ARUK Centre for Musculoskeletal Ageing Research, School of Biosciences, University of Nottingham, Sutton Bonington, UK.
Metabolism Unit, Shriners Hospitals for Children, Galveston, TX, USA.
BMC Musculoskelet Disord. 2019 Feb 11;20(1):70. doi: 10.1186/s12891-019-2452-0.
Preclinical osteoarthritis models where damage occurs spontaneously may better reflect the initiation and development of human osteoarthritis. The aim was to assess the commercial pig as a model of spontaneous osteoarthritis development by examining pain-associated behaviour, joint cartilage integrity, as well as the use of porcine cartilage explants and isolated chondrocytes and osteoblasts for ex vivo and in vitro studies.
Female pigs (Large white x Landrace x Duroc) were examined at different ages from 6 weeks to 3-4 years old. Lameness was assessed as a marker of pain-associated behaviour. Femorotibial joint cartilage integrity was determined by chondropathy scoring and histological staining of proteoglycan. IL-6 production and proteoglycan degradation was assessed in cartilage explants and primary porcine chondrocytes by ELISA and DMMB assay. Primary porcine osteoblasts from damaged and non-damaged joints, as determined by chondropathy scoring, were assessed for mineralisation, proliferative and mitochondrial function as a marker of metabolic capacity.
Pigs aged 80 weeks and older exhibited lameness. Osteoarthritic lesions in femoral condyle and tibial plateau cartilage were apparent from 40 weeks and increased in severity with age up to 3-4 years old. Cartilage from damaged joints exhibited proteoglycan loss, which positively correlated with chondropathy score. Stimulation of porcine cartilage explants and primary chondrocytes with either IL-1β or visfatin induced IL-6 production and proteoglycan degradation. Primary porcine osteoblasts from damaged joints exhibited reduced proliferative, mineralisation, and metabolic capacity.
In conclusion, the commercial pig represents an alternative model of spontaneous osteoarthritis and an excellent source of tissue for in vitro and ex vivo studies.
损伤自发发生的临床前骨关节炎模型可能更好地反映人类骨关节炎的起始和发展。目的是通过检查疼痛相关行为、关节软骨完整性，以及使用猪软骨外植体和分离的软骨细胞和成骨细胞进行体外和体内研究，评估商业猪作为自发骨关节炎发展模型的情况。
对6周龄至3 - 4岁不同年龄的雌性猪（大白猪×长白猪×杜洛克猪）进行检查。将跛行作为疼痛相关行为的指标进行评估。通过软骨病评分和蛋白聚糖的组织学染色来确定股胫关节软骨的完整性。通过酶联免疫吸附测定（ELISA）和二甲基甲亚苄基蓝（DMMB）测定法评估软骨外植体和原代猪软骨细胞中白细胞介素-6（IL-6）的产生和蛋白聚糖的降解。对通过软骨病评分确定的受损和未受损关节的原代猪成骨细胞进行矿化、增殖和线粒体功能评估，作为代谢能力的指标。
80周龄及以上的猪出现跛行。股骨髁和胫骨平台软骨的骨关节炎病变从40周龄开始明显，并随着年龄增长至3 - 4岁时严重程度增加。受损关节的软骨表现出蛋白聚糖丢失，这与软骨病评分呈正相关。用IL-1β或内脂素刺激猪软骨外植体和原代软骨细胞可诱导IL-6产生和蛋白聚糖降解。来自受损关节的原代猪成骨细胞表现出增殖、矿化和代谢能力降低。
总之，商业猪代表了自发骨关节炎的替代模型，也是体外和体内研究的优质组织来源。
