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Hyaluronan‐chondrocyte interactions mediate cell signaling pathways
Author(s) -
Luo Na,
Knudson Cheryl B,
Knudson Warren
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.953.5
Subject(s) - chondrocyte , cd44 , microbiology and biotechnology , cartilage , chemistry , signal transduction , mapk/erk pathway , cell , cancer research , biology , anatomy , biochemistry
Osteoarthritis is a degenerative process of articular cartilage. The focus of our project is to identify strategies to stimulate cartilage matrix repair. An intact, hyaluronan‐dependent pericellular matrix promotes the chondrocyte response to BMP‐7. Disruption of chondrocyte‐matrix interactions occurs during disease progression. The purpose of this study is to validate the function of CD44, the principal hyaluronan receptor, in mediating the effects of hyaluronan on chondrocyte signaling. Primary chondrocytes were isolated from 6–8 day old BALB/c mice and CD44 knock‐out (KO) mice, as well as adult bovine articular cartilage (CD44 positive). Testicular hyaluronidase (T H'ase) treatment of chondrocytes removed pericellular hyaluronan as visualized by immunostaining. Pre‐treatment with T H'ase stimulated Akt & ERK phosphorylation; this stimulation was muted by CD44 siRNA treatment of bovine chondrocytes. However, pre‐treatment with T H'ase reduced Smad1 phosphorylation and Id2 protein stimulation in response to BMP‐7 in all three chondrocyte models. Thus, in mouse chondrocytes, removal of hyaluronan has a profound effect on cell signaling pathways regardless of endogenous CD44 expression. Receptor compensation may occur in the CD44 KO chondrocytes or alternative mechanisms of hyaluronan‐cell interaction may influence these signaling pathways. Supported by NIH R01‐AR39507 and R01‐AR43384.