Proposed signaling interactions between CNP and mechanical signals in chondrocytes. C-type natriuretic peptide (CNP) binding to the natriuretic peptide receptor-B (NPR-B) activates the extracellular domain of guanylyl cyclase B (GC-B), leading to increased levels of 3,5'-cyclic guanosine monophosphate (cGMP). The accumulation of cGMP levels modulates the downstream activities of cGMP-dependent protein kinases (PKGI and II), cGMP-regulated ion channels (CGi), and cGMP-regulated phosphodiesterase (PDE) subtypes. PKGII mediates matrix synthesis augmented by mechanical signals that influence CGi ion channels. However, the cGMP pathways are likely to crosstalk with the catabolic pathways because of elevated levels of nitric oxide (NO) induced by interleukin-1β (IL-1β). More specifically, NO binds to the heme-containing soluble protein, guanylyl cyclase (sGC), and stimulates cGMP levels, which contribute to the production of PKGI or PDE subtypes, leading to matrix breakdown.