Basic fibroblast growth factor accelerates matrix degradation via a neuro-endocrine pathway in human adult articular chondrocytes.
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-1beta 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-1beta-dependent pathway.
Im
Hee-Jeong
HJ
Department of Biochemistry, Rush University Medical Center, Cohn Research BD, Chicago, Illinois 60612, USA. hee-jeong_sampen@rush.edu
Li
Xin
X
Muddasani
Prasuna
P
Kim
Gun-Hee
GH
Davis
Francesca
F
Rangan
Jayanthi
J
Forsyth
Christopher B
CB
Ellman
Michael
M
Thonar
Eugene J M A
EJ
D000328:Adult; D001172:Arthritis, Rheumatoid / Q000378:metabolism; D002358:Cartilage, Articular / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism*; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008660:Metabolism / Q000187:drug effects; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009490:Neurosecretory Systems / Q000378:metabolism*; D010003:Osteoarthritis / Q000378:metabolism; D011509:Proteoglycans / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D015398:Signal Transduction; D013373:Substance P / Q000378:metabolism / Q000494:pharmacology; D013582:Synovial Fluid / Q000378:metabolism; D013997:Time Factors; D015854:Up-Regulation; D048490:raf Kinases / Q000378:metabolism
D053583:Interleukin-1beta; D016328:NF-kappa B; D011509:Proteoglycans; D018040:Receptors, Neurokinin-1; D016222:Fibroblast Growth Factor 2; D013373:Substance P; D048490:raf Kinases; D020928:Mitogen-Activated Protein Kinases; D053509:Matrix Metalloproteinase 13; D020782:Matrix Metalloproteinases