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Publication : Carminerin contributes to chondrocyte calcification during endochondral ossification.

First Author  Yamada T Year  2006
Journal  Nat Med Volume  12
Issue  6 Pages  665-70
PubMed ID  16680148 Mgi Jnum  J:109550
Mgi Id  MGI:3629269 Doi  10.1038/nm1409
Citation  Yamada T, et al. (2006) Carminerin contributes to chondrocyte calcification during endochondral ossification. Nat Med 12(6):665-70
abstractText  Endochondral ossification is an essential process not only for physiological skeletal development and growth, but also for pathological disorders. We recently identified a novel cartilage-specific molecule, carminerin (also known as cystatin 10 and encoded by Cst10), which is upregulated in synchrony with cartilage maturation and stimulates the later differentiation of cultured chondrocytes. Although carminerin-deficient (Cst10(-/-)) mice developed and grew normally, they had a microscopic decrease in the calcification of hypertrophic chondrocytes at the growth plate. When we created experimental models of pathological endochondral ossification, we observed suppression of chondrocyte calcification during formation of osteoarthritic osteophytes, age-related ectopic ossification and healing of bone fractures in Cst10(-/-) mice. Cultured Cst10(-/-) chondrocytes showed a reduction in calcification with activation of an SRY site in the promoter of the gene encoding nucleotide pyrophosphatase phosphodiesterase 1 (NPP1, encoded by Enpp1). Functional NPP1 is required for carminerin deficiency to suppress the pathological endochondral ossifications listed above. Carminerin is the first cartilage-specific protein that contributes to chondrocyte calcification during endochondral ossification under physiological and pathological conditions through the transcriptional inhibition of NPP1.
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