Journal
JOURNAL OF CELLULAR PHYSIOLOGY
Volume 215, Issue 2, Pages 452-463Publisher
WILEY
DOI: 10.1002/jcp.21317
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Funding
- VA [726287, 1I01BX002647-01] Funding Source: Federal RePORTER
- NIAMS NIH HHS [R01 AR053220-04, R01 AR053220] Funding Source: Medline
- BLRD VA [I01 BX002647] Funding Source: Medline
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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-I tachykinin receptor (NK1-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-1 beta accelerate matrix degradation via a neural pathway upregulation of substance P and NK1-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 NK1-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 NK1-R is, in part, through an IL-1 beta-dependent pathway.
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