Protective Effects of C‐Type Natriuretic Peptide on Linear Growth and Articular Cartilage Integrity in a Mouse Model of Inflammatory Arthritis
Open Access
- 24 September 2013
- journal article
- research article
- Published by Wiley in Arthritis & Rheumatology
- Vol. 66 (1), 78-89
- https://doi.org/10.1002/art.38199
Abstract
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. Conclusion 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.Keywords
This publication has 52 references indexed in Scilit:
- Evaluation of the Therapeutic Potential of a CNP Analog in a Fgfr3 Mouse Model Recapitulating AchondroplasiaAmerican Journal of Human Genetics, 2012
- Pomegranate extract inhibits the interleukin-1β-induced activation of MKK-3, p38α-MAPK and transcription factor RUNX-2 in human osteoarthritis chondrocytesArthritis Research & Therapy, 2010
- C-natriuretic peptide: An important regulator of cartilageMolecular Genetics and Metabolism, 2007
- Overexpression of the C-type natriuretic peptide (CNP) is associated with overgrowth and bone anomalies in an individual with balanced t(2;7) translocationHuman Mutation, 2007
- C-type natriuretic peptide regulates endochondral bone growth through p38 MAP kinase-dependent and – independent pathwaysBMC Developmental Biology, 2007
- C-type natriuretic peptide in vascular physiology and diseasePharmacology & Therapeutics, 2005
- Mutations in the Transmembrane Natriuretic Peptide Receptor NPR-B Impair Skeletal Growth and Cause Acromesomelic Dysplasia, Type MaroteauxAmerican Journal of Human Genetics, 2004
- Inhibition of Cyclooxygenase-2 by Natriuretic PeptidesEndocrinology, 2002
- Glucocorticoid treatment or food deprivation counteract the stimulating effect of growth hormone on rat cortical bone strengthActa Paediatrica, 1992
- Growth Abnormalities in Children With Juvenile Rheumatoid ArthritisClinical Orthopaedics and Related Research, 1990