Structural, compositional and functional changes of joint tissues in a long-term equine carpal groove model featuring blunt and sharp cartilage damage

Background Osteoarthritis (OA) affects millions of people and animals worldwide. Better insight is needed into the effects of articular cartilage damage, the interaction between the various joint tissues, and how they influence overall joint health, to help timely recognition of OA and to reveal new treatment targets. We aimed to quantify the longer-term progression of artificially created blunt and sharp cartilage grooves and their effect on other joint tissues in the equine carpal joint by multiple modality monitoring. Methods For 9 adult female Shetland ponies, the cartilage in the radiocarpal and middle carpal joint was grooved (one blunt and one sharp) via arthrotomy. The contra-lateral joint was sham-operated. After 3 weeks of box rest, the ponies were trained for 8 weeks on a treadmill. Following upon groove surgery and during follow-up arthroscopies at 11, 23 and 39 weeks, intra-articular optical coherence tomography and near infrared spectroscopy measurements were performed and synovial biopsies were taken for microscopic and gene expression analysis. Synovial fluid was obtained prior to each surgery and at week 19 and 35 for biomarker measurements. Radiographs of both carpi were taken at baseline and at 38 weeks and consecutive optical motion capture data was collected during the study. At 39 weeks, ponies were euthanized, and osteochondral samples were harvested. Macroscopic and microscopic changes of the articular cartilage were scored according to OARSI guidelines. Cartilage thickness and subchondral bone parameters were calculated from micro-CT images. Biomechanical properties of the cartilage were determined by indentation testing. Results Blunt and sharp grooves led to degenerative changes of the articular cartilage, quantified by higher OARSI scores at microscopy compared with control joints (p<0.0001). Blunt-grooved cartilage scored higher than sharp-grooved cartilage (p = 0.007) and showed more loss of collagen type 2 around the defect. Cartilage thickness did not differ between grooved and control joints, but cartilage equilibrium and instantaneous moduli trended lower in grooved joints, being significant for sharp-grooved cartilage (p = 0.002 and p = 0.045, respectively). Concomitant changes in other articular tissues remained limited to increased radiographic scores in grooved joints at 38 weeks (p = 0.007), significantly increased IL-6, CCL2, and ALK5 expression levels compared to baseline in synovium from grooved joints, and an increased CPII/ C2C ratio in SF from blunt-grooved joints at week 35 (p = 0.03). No differences in the subchondral bone were found. Quantitative gait analysis was consistent with a mild, gradually increasing bilateral lameness. Conclusions Both blunt and sharp articular cartilage grooves in the equine carpal joint, in combination with a period of intensified loading, lead to degenerative changes over a 9-month period. However, the overall effect on joint homeostasis and function in terms of gait quality remained limited. We hypothesize that it is the combination of lesion morphology, together with the loading profile that will determine the speed and characteristics of progression of further degeneration.