Protective effects of C-type natriuretic peptide on linear growth and articular cartilage integrity in a mouse model of inflammatory arthritis.
OBJECTIVE
The C-type natriuretic peptide (CNP) signaling pathway is a major contributor to postnatal skeletal growth in humans. This study was undertaken to investigate whether CNP signaling could prevent growth delay and cartilage damage in an animal model of inflammatory arthritis.


METHODS
We generated transgenic mice that overexpress CNP (B6.SJL-Col2a1-NPPC) in chondrocytes. We introduced the CNP transgene into mice with experimental systemic inflammatory arthritis (K/BxN T cell receptor [TCR]) and determined the effect of CNP overexpression in chondrocytes on the severity of arthritis, cartilage damage, and linear growth. We also examined primary chondrocyte cultures for changes in gene and protein expression resulting from CNP overexpression.


RESULTS
K/BxN TCR mice exhibited linear growth delay (P < 0.01) compared to controls, and this growth delay was correlated with the severity of arthritis. Diminished chondrocyte proliferation and matrix production was also seen in K/BxN TCR mice. Compared to non-CNP-transgenic mice, K/BxN TCR mice with overexpressed CNP had milder arthritis, no growth delay, and less cartilage damage. Primary chondrocytes from mice overexpressing CNP were less sensitive to inflammatory cytokines than wild-type mouse chondrocytes.


CONCLUSIONS
CNP overexpression in chondrocytes can prevent endochondral growth delay and protect against cartilage damage in a mouse model of inflammatory arthritis. Pharmacologic or biologic modulation of the CNP signaling pathway may prevent growth retardation and protect cartilage in patients with inflammatory joint diseases, such as juvenile idiopathic arthritis.
MetroHealth Medical Center and Case Western Reserve University, Cleveland, Ohio.
Hülya
H
Bükülmez
Fozia
F
Khan
Cynthia F
CF
Bartels
Shunichi
S
Murakami
Adriana
A
Ortiz-Lopez
Abdus
A
Sattar
Tariq M
TM
Haqqi
Matthew L
ML
Warman
D000818:Animals; D001169:Arthritis, Experimental / Q000378:metabolism / Q000503:physiopathology*; D001171:Arthritis, Juvenile / Q000378:metabolism / Q000503:physiopathology; D001846:Bone Development / Q000502:physiology*; D002358:Cartilage, Articular / Q000254:growth & development* / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D019902:Chondrocytes / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D020098:Natriuretic Peptide, C-Type / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
D020098:Natriuretic Peptide, C-Type