Proteoglycan inhibition of canonical BMP-dependent cartilage maturation delays endochondral ossification.

Autor:	Koosha E; Department of Anatomy, Physiology, and Pharmacology, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada., Brenna CTA; Department of Anatomy, Physiology, and Pharmacology, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada., Ashique AM; Department of Anatomy, Physiology, and Pharmacology, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada., Jain N; Department of Anatomy, Physiology, and Pharmacology, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada., Ovens K; Department of Computer Science, University of Calgary, Calgary, AB T2N 1N4, Canada., Koike T; Department of Biochemistry, Kobe Pharmaceutical University, Higashinada-ku, Kobe 658-0003, Japan., Kitagawa H; Department of Biochemistry, Kobe Pharmaceutical University, Higashinada-ku, Kobe 658-0003, Japan., Eames BF; Department of Anatomy, Physiology, and Pharmacology, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada.
Jazyk:	angličtina
Zdroj:	Development (Cambridge, England) [Development] 2024 Jan 15; Vol. 151 (2). Date of Electronic Publication: 2024 Jan 12.
DOI:	10.1242/dev.201716
Abstrakt:	During endochondral ossification, chondrocytes secrete a proteoglycan (PG)-rich extracellular matrix that can inhibit the process of cartilage maturation, including expression of Ihh and Col10a1. Because bone morphogenetic proteins (BMPs) can promote cartilage maturation, we hypothesized that cartilage PGs normally inhibit BMP signalling. Accordingly, BMP signalling was evaluated in chondrocytes of wild-type and PG mutant (fam20b-/-) zebrafish and inhibited with temporal control using the drug DMH1 or an inducible dominant-negative BMP receptor transgene (dnBMPR). Compared with wild type, phospho-Smad1/5/9, but not phospho-p38, was increased in fam20b-/- chondrocytes, but only after they secreted PGs. Phospho-Smad1/5/9 was decreased in DMH1-treated or dnBMPR-activated wild-type chondrocytes, and DMH1 also decreased phospho-p38 levels. ihha and col10a1a were decreased in DMH1-treated or dnBMPR-activated chondrocytes, and less perichondral bone formed. Finally, early ihha and col10a1a expression and early perichondral bone formation of fam20b mutants were rescued with DMH1 treatment or dnBMPR activation. Therefore, PG inhibition of canonical BMP-dependent cartilage maturation delays endochondral ossification, and these results offer hope for the development of growth factor therapies for skeletal defects of PG diseases. Competing Interests: Competing interests The authors declare no competing or financial interests. (© 2024. Published by The Company of Biologists Ltd.)
Databáze:	MEDLINE
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