Abstract
Osteoarthritis (OA) is a ubiquitous disease affecting many horses. The disease causes chronic pain and decreased performance for patients and great cost to owners for diagnosis and treatment. The most common treatments include systemic non-steroidal anti-inflammatory drugs and intra-articular injection of corticosteroids. There is excellent support for the palliative pain relief these treatments provide; however, they do not arrest progression and may in some instances hasten advancement of disease. Orthobiologic treatments have been investigated as potential OA treatments that may not only ameliorate pain but also prevent or reverse pathologic articular tissue changes. Clinical protocols for intra-articular use of such treatments have not been optimized; the high cost of in vivo research and concerns over humane use of research animals may be preventing discovery. The objective of this study was to evaluate a novel in vitro articular coculture system for future use in OA treatment research. Concentrations and fold increases in various markers of inflammation (prostaglandin E2 and tumor necrosis factor-alpha), degradative enzyme activity [matrix metalloproteinase-13 (MMP-13)], cartilage and bone metabolism (bone alkaline phosphatase and dimethyl-methylene blue), and cell death (lactate dehydrogenase) were compared between IL-1-stimulated equine articular cartilage explant cultures and cocultures comprised of osteochondral and synovial explants (OCS). Results suggested that there are differences in responses of culture systems to inflammatory stimulation. In particular, the IL-1-induced fold changes in MMP-13 concentration were significantly different between OCS and cartilage explant culture systems after 96 h. These differences may be relevant to responses of joints to inflammation in vivo and could be important to the biological relevance of in vitro research findings.
Highlights
Osteoarthritis (OA)-related joint pain affects a large proportion of the horse population resulting in chronic pain, decreased mobility, decreased performance, reduced quality of life, and high owner expense [1, 2]
In response to IL-1 stimulation, both osteochondral and synovial explants (OCS) and cartilage explant cultures had an increase in prostaglandin E2 (PGE2) concentration
The magnitude of the increase in PGE2 concentration was similar at each time point for OCS and cartilage cultures
Summary
Osteoarthritis (OA)-related joint pain affects a large proportion of the horse population resulting in chronic pain, decreased mobility, decreased performance, reduced quality of life, and high owner expense [1, 2]. Effects of IL-1 on Equine Cartilage versus OCS treatments are only palliative and do not modify the progression of OA. Long-term NSAID use carries potentially serious side effects and corticosteroids may cause negative sequelae in articular cartilage [3]. Orthobiologics (commonly termed regenerative therapies) have been used as potentially safer and more efficacious alternatives. Orthobiologic techniques available for use in domestic animals include platelet-rich plasma, autologous conditioned serum [ known as IL-1 receptor antagonist protein (IL-1ra)], and autologous or allogeneic stem cells. Such treatments can improve function of equine joints [4,5,6]. There is a need for further research to refine clinical use of such therapies
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