|Budget Amount *help
¥2,100,000 (Direct Cost : ¥2,100,000)
Fiscal Year 1995 : ¥900,000 (Direct Cost : ¥900,000)
Fiscal Year 1994 : ¥1,200,000 (Direct Cost : ¥1,200,000)
I investigated the effects of vasoactive peptides, natriuretic peptides (NP) and endothelin (ET) on cartilaginous metabolism. C-type natriuretic peptide (CNP) and B-type natriuretic peptide receptor (NPR-B) were present in cultured chondrocytes derived from rat xiphoid cartilage. Autocine CNP inhibited mitogenesis in chondrocytes via NPR-B under the control of TGF-beta and was involved in in vitro dedifferentiation. Furthermore, subtype switching of NPR during in vitro culture of rat chondrocytes was demonstrated by polymerase chain reaction analysis, receptor binding assay, and the cGMP formation method. Next, I examined the localization and characterization of endothelin receptor subtype in rat cartilages. Autoradiographic studies using ^<125>I-labeled endothelin-1 (ET-1) on sections of rat cartilage tissues, including the trachea, xiphisternum, and fetal rat epiphysis, revealed dense localization of endothelin receptors in the perichondrium. The perichondrial binding of ^<125>I-ET-1 was completely abolished wit BQ-123 (an endothelin receptor subtype A antagonist).Therefore, we demostrated the perichondrial localization of ETA receptors. [^3H] thymidine incorporation in vitro was significantly increased in rat xiphoid cartilage tissues exposed to ET-1.
These results suggest that NP system and ET system plays an important role in regulating cartilage metabolism and endochondral bone formation.