ISSN 1662-4009 (online)

ESPE Yearbook of Paediatric Endocrinology (2022) 19 5.13 | DOI: 10.1530/ey.19.5.13

ESPEYB19 5. Bone, Growth Plate and Mineral Metabolism Translational highlights (6 abstracts)

5.13. C-type natriuretic peptide-induced PKA activation promotes endochondral bone formation in hypertrophic chondrocytes

Hirota K , Hirashima T , Horikawa K , Yasoda A & Matsuda M


Department of Pathology and Biology of Diseases, Graduate School of Medicine, Kyoto University, Kyoto, Japan


Endocrinology 163, bqac005. (2022).Abstract: https://pubmed-ncbi-nlm-nih-gov/35041746/

In Brief: C-type natriuretic peptide (CNP) is known to stimulate enchondral bone formation, but the distinct cellular pathways and cellular targets are unclear. This study used in vivo and in vitro biosensor systems to identify cGMP-induced activation of PKA as a major effect of CNP with growth promoting effects in hypertrophic growth plate chondrocytes.

Commentary: C-type natriuretic peptide (CNP) represents an important anabolic regulator of endochondral bone growth affecting chondrocyte proliferation, hypertrophy and matrix production. Although the stimulation of enchondral bone formation is already clinically used in the treatment of patients with achondroplasia, the precise mechanism and cellular targets within the growth plate are not entirely elucidated.

These authors used FRET-based cGMP and PKA biosensors to show that CNP both increased intracellular cGMP levels and stimulated PKA activity in transfected ATDC5 chondrocytes. In contrast to cGMP stimulation, CNP-induced PKA activation was enhanced during differentiation. Live imaging of growth plates in radial explants of mice expressing a FRET PKA biosensor revealed CNP-associated activation mainly in the hypertrophic zone. Increased growth plate length under CNP treatment was specifically inhibited in hypertrophic cells by PKA-inhibitor cotreatment, indicating a differentiation specific effect of CNP-induced PKA activation.

In summary, Hirota et al identified PKA-activation in the hypertrophic zone as part of the growth-promoting effect of CNP. These data pave the way for future studies on the CNP-induced cross-talk between cGMP and cAMP signaling and interaction with other regulatory pathways.

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