Table 2.
- Effect of putative DMOADs on joint structure and pain assessments
| Target/Compound | Model | Effect on Joint Pathology | Changes in Nociception/Pain Outcomes reported | Ref. | Comments |
|---|---|---|---|---|---|
| MMP-13 (selective inhibitor) | Rat MIA 2-week follow up | Cartilage protection | Prevention of changes in weight-bearing | [103] | In the same paper, the same compound had chondroprotective effects in the rat MMT model, but effects on associated pain were not analyzed. |
| ADAMTS-4/ADAMTS-5 selective inhibitor | Rat MMT 13-week follow-up | Cartilage protection | Prevention of changes in weight-bearing | [104] | |
| ADAMTS-5 KO mice | Mouse DMM 8-week follow-up | No OA-like pathology | No development of secondary mechanical allodynia (unlike wild type mice, which develop progressive allodynia) | [52] | |
| Cathepsin K (selective inhibitor) | Guinea Pig spontaneous 1-month follow-up | Decreased urinary CTXII (marker of type II collagen degradation) | Reduced mechanosensitivity (elctrophysiologically determined) in response to noxious and non-noxious joint movement | [105] | Cathepsin K inhibition has recently gathered attention as a promising target for structure modification in OA, and selective inhibitors have proven efficacious in canine, mouse, and rabbit models of OA [106, 107]. |
| Biphosphonates: | |||||
| zoledronate | Rat MIA | Protective effect against all MIA-induced joint changes | Ameliorated changes in weight-bearing | [108] | The effect of prophylactic and therapeutic zoledronate at different time point post MIA were compared |
| tiludronate | Dog ACLT, 8-week follow-up | Some beneficial effects on joint changes (including subchondral bone and synovitis) | Positive effect on gait changes and joint symptoms (a composite numerical rating scale (NRS), visual analog scale, and electrodermal activity) | [98] | Treatment commenced at the time of surgery |
| Angiogenesis blocker, PPI-2458 | Rat MMT 5-week follow-up | Reduced joint damage and synovitis | Reduced changes in weight-bearing | [70] | This compound is a fumagillin analog that triggers growth arrest of endothelial cells in the G1 phase. |
| Intra-articular recombinant human lubricin with a truncated mucin-like domain (LUB-1) | Rat MMT 5-week follow-up | Reduced cartilage degradation (no changes in subchondral bone) | Ameliorated reduced weight-bearing on operated limb | [109, 110] | IA administration of LUB-1 started one week after surgery |
| GM-CSF blocking antibody | Mouse CoiA 6-week follow-up | Reduced cartilage damage Reduced synovitis | Ameliorated changes in weight-bearing | [102] | Antibodies were efficacious in a therapeutic and in a prophylactic protocol |
Abbreviations: MIA - monoiodoacetate-induced arthritis, MMT - medial meniscal transection, DMM = destabilization of the medial meniscus, ACLT - anterior (or cranial in dog) cruciate ligament transection, MNX = meniscectomy, CoiA = collagenase-induced arthritis.