Gene expression analysis of subchondral bone, cartilage, and synovium in naturally occurring equine palmar/plantar osteochondral disease
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Publisher URL
DOI
10.1002/jor.25075
Journal
JOURNAL OF ORTHOPAEDIC RESEARCH
ISSN
0736-0266
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Osteoarthritis (OA) is a disease of the entire joint but the relationship betweenpathological events in various joint tissues is poorly understood. We examinedconcurrent changes in bone, cartilage, and synovium in a naturally occurring equinemodel of joint degeneration. Joints (n = 64) were grossly assessed for palmar/plantarosteochondral disease (POD) in racehorses that required euthanasia for unrelatedreasons and assigned a grade of 0 (n = 34), 1 (n = 17), 2 or 3 (n = 13) using a re-cognized grading scheme. Synovium, cartilage, and subchondral bone were collectedfor histological and gene expression analysis. Relations between POD grade, carti-lage histological score, and gene expression levels were examined using onewayanalysis of variance or Kruskal–Wallis test and Spearman's correlation coefficientwith corrections for multiple comparisons. Cartilage histological score increased injoints with POD grade 1 (p = 0.002) and 2 or 3 (p < 0.001) compared to 0. At grade 1,expression of COL1A1, COL2A1, and MMP1 increased and BGN decreased insubchondral bone while expression of BGN and ACAN decreased in cartilage. Thesechanges further progressed at grades 2 and 3. POD grades 2 and 3 were associatedwith decreased expression of osteoclast inhibitor OPG and increased markers ofcartilage degeneration (MMP13, COL1A1). Expression of the vascular endothelialgrowth factor decreased with POD grade and negatively correlated with cartilage histological score. Synovium showed no histological or transcriptomic changes re-lated to pathology grade. Cartilage degeneration in POD is likely to be secondary toremodeling of the subchondral bone. Limited activation of proinflammatory andcatabolic genes and moderate synovial pathology suggests distinct molecularphenotype of POD compared with OA.