Cartilage-protective effects of C-type natriuretic peptide over expression in K/BxN TCR arthritis model
Year: 2012
Type: article
Abstract: We first developed transgenic mice that over-express CNP ( CNP ) in chondrocytes under the control of the collagen 2a1 promoter and enhancer. Then, we obtained K/BxN TCR transgenic mice from a collaborator and analyzed both transgenic mice for their joint cartilage clinical and histologic findings over time. We crossed CNP mouse with K/BxN TCR transgenic mouse to produce mice with both K/BxN TCR and CNP backgrounds. The degree of arthritis and cartilage damage in the offspring was analyzed using a clinical scoring system and two histological scoring systems. Differences between the scores were analyzed using the Student’s t-test. Mice that carried the transgene for both CNP and K/BxN TCR showed less severe clinical and histologic arthritis findings in the joint cartilage compared to wild type littermates. Between the ages of 6-14 weeks, the average arthritis score of K/BxN TCR transgenic mice that over-expressed CNP was 4.37 ±1.38 (n=8), while the average arthritis score of K/BxN TCR arthritic mice of the same age was 8.66 ±3.26 (n=14), (p<0.05). Histological staining and morphometry did not show any evidence of cartilage degradation in the joint cartilage of CNP mice. The knee and ankle cartilage of CNP mice was thick and showed increased proteoglycan content by Safranin-O staining. However, the double-transgenic offspring mice (K/BxN/CNP ) developed less cartilage damage and less chondrocyte disorganization while still developing inflammatory changes (pannus) in the synovium, similar to the K/BxN TCR mice. We adapted the ICRS histological scoring system and gave scores to the knee joint cartilage of the 8-week-old male mice. K/BxN mice (n=7) scored significantly lower for both chondrocytic cell distribution (III) and chondrocyte matrix content (II) (p<0.001 and p<0.05, respectively) than the (K/BxN/ CNP mice (n=12). K/BxN TCR arthritic mice over-expressing CNP did not have joint cartilage damage due to chronic inflammation. We conclude that excess paracrine production of CNP in the joint cartilage of double-transgenic K/BxN/CNP arthritic mice was able to overcome the effects of pro-inflammatory cytokines on joint cartilage in vivo . CNP and the effector molecules of CNP signaling pathway may have therapeutic potential in protecting cartilage homeostasis during chronic inflammatory arthritis.
Source: Pediatric Rheumatology
Language: English
Subfield: Rheumatology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,090
OpenAlex ID: W31218241