Local Blockade of CCL21 and CXCL13 Signaling as a New Strategy to Prevent and Treat Osteoarthritis
Technical Report,01 Aug 2015,30 Aug 2016
Loma Linda Veterans Association for Research and Education Redlands United States
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Osteoarthritis is the most prevalent type of arthritis. It is characterized by progressive cartilage loss, synovialin flammation, with resultant joint pain that worsens over time.While meniscectomy appears to be a significant risk factor for OA, researchers know little about the molecular pathways involved in the induction and development of osteoarthritis. In the present study, we proposed to investigate the role of the chemokines Ccl21 and Cxcl13 in inflammation caused by medial meniscectomy-knee destabilization MMD that leads to osteoarthritis. Therefore, we first evaluated the expression profile of these two chemokines in response to MMD in a rat knee injury model. mRNA levels for both chemokines were increased at 3 days and one week post-surgery. However, only Ccl21 mRNA levels were significantly elevated in MMD knees compared to sham operated knees at 4 weeks post-surgery. This suggests that Cxcl13 is only involved in the first stages of osteoarthritis development, while Ccl21 is involved in both the early inflammation and the later stages of osteoarthritis development. Histological analysis revealed proteoglycan loss in the superficial zone of the articular cartilage that was obvious at 4 weeks post-surgery and in the calcified zone by 6 weeks post-surgery. These data confirm the involvement of CCL21 in cartilage catabolism. We are currently analyzing histological sections that were immune-stained to detect T and B cell markers, in order determine if there is a correlation between the expression of Cxcl13 and Ccl21, and the infiltration of inflammatory cells that occurs following knee surgery.
- Genetic Engineering and Molecular Biology
- Anatomy and Physiology
- Medicine and Medical Research