Muscle cells enhance resistance to pro-inflammatory cytokine-induced cartilage destruction.
Pro-inflammatory cytokines IL-1beta and TNFalpha play important roles in the manifestation of arthritis by disrupting the anabolic and catabolic activities of the chondrocytes. We observed a novel mechanism of cartilage regulation by which muscle cells diminish the response of chondrocytes to IL-1beta and TNFalpha. We found that chondrocytes cocultured with muscle cells or cultured in muscle cell-conditioned medium significantly enhanced the expression of cartilage matrix proteins (collagen II and collagen IX) and resisted IL-1beta and TNFalpha-induced cartilage damage. Our data suggest that this effect is achieved by inhibiting the expression of key components of the signaling pathways of pro-inflammatory cytokines (including NFkappaB, ESE-1, Cox-2, and GADD45beta), leading to attenuated expression of cartilage-degrading enzymes (MMPs and ADAMTS4). Therefore, our work unveils a potential role of muscle in regulating cartilage homeostasis and response to pro-inflammatory stimuli, and provides insights on designing treatment strategies for joint degenerative diseases such as arthritis.
Cairns
Dana M
DM
Program in Cellular, Molecular and Developmental Biology, Sackler School of Graduate Biomedical Sciences, Tufts University, 136 Harrison Avenue, Boston, MA 02111, USA.
Uchimura
Tomoya
T
Kwon
Heenam
H
Lee
Philip G
PG
Seufert
Christopher R
CR
Matzkin
Elizabeth
E
Zeng
Li
L
D051722:ADAM Proteins / Q000378:metabolism; D000071121:ADAMTS4 Protein; D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism; D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D002358:Cartilage, Articular / Q000187:drug effects / Q000378:metabolism*; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism*; D018920:Coculture Techniques; D003094:Collagen / Q000096:biosynthesis; D051546:Cyclooxygenase 2 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism* / Q000494:pharmacology; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D032446:Myoblasts / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D041681:NIH 3T3 Cells; D010003:Osteoarthritis / Q000378:metabolism*; D011348:Procollagen N-Endopeptidase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism* / Q000494:pharmacology; D000097642:GADD45 Proteins
D051722:ADAM Proteins; D000071121:ADAMTS4 Protein; D033942:Adaptor Proteins, Vesicular Transport; D000943:Antigens, Differentiation; D003094:Collagen; D051546:Cyclooxygenase 2; D053583:Interleukin-1beta; D053509:Matrix Metalloproteinase 13; D020780:Matrix Metalloproteinase 9; D016328:NF-kappa B; D011348:Procollagen N-Endopeptidase; D014409:Tumor Necrosis Factor-alpha; C490125:Gadd45b protein, mouse; D000097642:GADD45 Proteins; C118534:Itsn protein, mouse; C077623:Ptgs2 protein, mouse; C507081:Mmp13 protein, mouse; C501830:Mmp9 protein, mouse; C000603919:Adamts4 protein, mouse