00741: Polymicrobial Bacteria-Associated Inflammatory Stifle Arthritis/Degenerative Cranial Cruciate Ligament Rupture in Dogs
Grant Status: Closed
Pathological or degenerative rupture of the cranial cruciate ligament (CCLR) in the stifle joint of the dog is a progressive condition that is often bilateral and is not associated with obvious trauma. In human beings, this ligament is referred to as the anterior cruciate ligament or ACL in the knee joint. Historically, it has been thought that stifle arthritis in dogs develops because of joint instability, joint instability develops because of CCLR and CCLR develops because of trauma. There is now strong evidence that this paradigm is not correct. Work we have conducted with the support of the AKC Canine Health Foundation suggests that CCLR is preceded by development of chronic inflammation and arthritis in the stifle joint in the majority of affected dogs. Our long-range goal is to develop safe and effective therapies that will reduce inflammation within the stifle of affected dogs, prevent progressive degradation of the affected CCL and potentially enable CCL healing in dogs that have experienced ligament tearing and rupture. With the support of the Canine Health Foundation, over the last six months, we have moved several steps closer to our goal. By evaluating affected dogs clinically and conducting detailed analyses of joint tissues collected during surgical treatment of client-owned dogs, we have shown that stifle arthritis precedes development of joint instability associated with CCLR. Furthermore, development of arthritis precedes fraying of the CCL in affected dogs with stable stifles. We have also found that small amounts of bacterial material are commonly found in affected arthritic stifles, although the presence of this material is not highly correlated with clinical markers of joint inflammation. Detailed analysis of the population of inflammatory cells within joint tissues of affected stifles suggests that joint immune responses are activated by a specific protein trigger referred to as an antigen. This type of pathology is typical of other rheumatic diseases, such as rheumatoid arthritis or reactive arthritis in human beings. Because the amount of bacterial material in the stifle joint lining of affected dogs is not highly related to the severity of the inflammation in the joint, it seems likely that a specific factor (likely genetic) makes dogs susceptible and enables joint antigens, such as bacterial material or proteins derived from ligament or cartilage, to trigger joint inflammation in specific individual dogs. We have preliminary data to support this concept and now wish to study this question further in future work. Also, in future work, we believe that the inflammatory cells in affected joints, particularly the type of cell referred to as a T lymphocyte, may represent an important therapeutic target for drug treatment. By treating the joint inflammation with a disease-modifying medical therapy, it may be possible to block joint degeneration over time and reduce the incidence of cruciate rupture in affected dogs.
Muir, P., Fox, R., Wu, Q., Baker, T. A., Zitzer, N. C., Hudson, A. P., … Hao, Z. (2010). Seasonal variation in detection of bacterial DNA in arthritic stifle joints of dogs with cranial cruciate ligament rupture using PCR amplification of the 16S rRNA gene. Veterinary Microbiology, 141(1–2), 127–133. https://doi.org/10.1016/j.vetmic.2009.08.015
Muir, P., Kelly, J. L., Marvel, S. J., Heinrich, D. A., Schaefer, S. L., Manley, P. A., … Plisch, E. (2011). Lymphocyte Populations in Joint Tissues from Dogs with Inflammatory Stifle Arthritis and Associated Degenerative Cranial Cruciate Ligament Rupture: Lymphocyte Populations in Joint Tissues. Veterinary Surgery, 40(6), 753–761. https://doi.org/10.1111/j.1532-950X.2011.00867.x
Muir, P., Oldenhoff, W. E., Hudson, A. P., Manley, P. A., Schaefer, S. L., Markel, M. D., & Hao, Z. (2007). Detection of DNA from a range of bacterial species in the knee joints of dogs with inflammatory knee arthritis and associated degenerative anterior cruciate ligament rupture. Microbial Pathogenesis, 42(2–3), 47–55. https://doi.org/10.1016/j.micpath.2006.10.002
Schwartz, Z., Zitzer, N. C., Racette, M. A., Manley, P. A., Schaefer, S. L., Markel, M. D., … Muir, P. (2011). Are bacterial load and synovitis related in dogs with inflammatory stifle arthritis? Veterinary Microbiology, 148(2–4), 308–316. https://doi.org/10.1016/j.vetmic.2010.09.011
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