title: Carminerin contributes to chondrocyte calcification during endochondral ossification.
abstract: 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.
authors: Department of Sensory & Motor System Medicine, Faculty of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo, Tokyo 113-8655, Japan.
authors: Takashi
authors: T
authors: Yamada
authors: Hirotaka
authors: H
authors: Kawano
authors: Yu
authors: Y
authors: Koshizuka
authors: Toru
authors: T
authors: Fukuda
authors: Kimihiro
authors: K
authors: Yoshimura
authors: Satoru
authors: S
authors: Kamekura
authors: Taku
authors: T
authors: Saito
authors: Toshiyuki
authors: T
authors: Ikeda
authors: Yosuke
authors: Y
authors: Kawasaki
authors: Yoshiaki
authors: Y
authors: Azuma
authors: Shiro
authors: S
authors: Ikegawa
authors: Kazuto
authors: K
authors: Hoshi
authors: Ung-il
authors: UI
authors: Chung
authors: Kozo
authors: K
authors: Nakamura
authors: Shigeaki
authors: S
authors: Kato
authors: Hiroshi
authors: H
authors: Kawaguchi