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Basic fibroblast growth factor accelerates matrix degradation via a neuro‐endocrine pathway in human adult articular chondrocytes
Author(s) -
Im HeeJeong,
Li Xin,
Muddasani Prasuna,
Kim GunHee,
Davis Francesca,
Rangan Jayanthi,
Forsyth Christopher B.,
Ellman Michael,
Thonar Eugene JMA
Publication year - 2008
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.21317
Subject(s) - substance p , chemistry , microbiology and biotechnology , endocrinology , proteoglycan , medicine , receptor , cartilage , fibroblast growth factor , growth factor , biology , neuropeptide , extracellular matrix , biochemistry , anatomy
Pain‐related neuropeptides released from synovial fibroblasts, such as substance P, have been implicated in joint destruction. Substance P‐induced inflammatory processes are mediated via signaling through a G‐protein‐coupled receptor, that is, neurokinin‐1 tachykinin receptor (NK 1 ‐R). We determined the pathophysiological link between substance P and its receptor in human adult articular cartilage homeostasis. We further examined if catabolic growth factors such as basic fibroblast growth factor (bFGF or FGF‐2) or IL‐1β accelerate matrix degradation via a neural pathway upregulation of substance P and NK 1 ‐R. We show here that substance P stimulates the production of cartilage‐degrading enzymes, such as matrix metalloproteinase‐13 (MMP‐13), and suppresses proteoglycan deposition in human adult articular chondrocytes via NK 1 ‐R. Furthermore, we have demonstrated that substance P negates proteoglycan stimulation promoted by bone morphogenetic protein‐7, suggesting the dual role of substance P as both a pro‐catabolic and anti‐anabolic mediator of cartilage homeostasis. We report that bFGF‐mediated stimulation of substance P and its receptor NK 1 ‐R is, in part, through an IL‐1β‐dependent pathway. J. Cell. Physiol. 215: 452–463, 2008. © 2007 Wiley‐Liss, Inc.