A novel chordin-like BMP inhibitor, CHL2, expressed preferentially in chondrocytes of developing cartilage and osteoarthritic joint cartilage

• DOI: 10.1242/dev.00901
• Publication Date: 2003-12-09T01:12:49Z
• Authors: Naoki Nakayama; Chun-ya E. Han; Linh Cam; Jae I. Lee; Jim Pretorius; Seth Fisher; Robert Rosenfeld; Sheila Scully; Ryuichi Nishinaka...; Diane Duryea; Gwyneth Van; Brad Bolon; Takashi Yokota; Ke Zhang
• Keywords: Chondrogenesis; Hyaline cartilage; Chordin; Perichondrium

We have identified a novel chordin-like protein, CHL2, which is structurally most homologous to CHL/neuralin/ventroptin. When injected into Xenopus embryos, CHL2 RNA induced secondary axis. Recombinant protein interacted directly with BMPs in competitive manner prevent binding the type I BMP receptor ectodomain, and inhibited BMP-dependent induction of alkaline phosphatase C2C12 cells. Thus, behaves as secreted BMP-binding inhibitor. In situ hybridization revealed that expression restricted chondrocytes various developing joint cartilage surfaces connective tissues reproductive organs. Adult mesenchymal progenitor cells expressed its levels decreased during chondrogenic differentiation. Addition culture system reduced matrix deposition. Consistently, transcripts were weakly detected normal adult cartilage. However, was upregulated middle zone osteoarthritic (where hypertrophic markers are induced). depressed chondrocyte mineralization when added differentiation cultured hyaline particles. may play negative roles (re)generation maturation articular both degenerated joints.