The role of osteopontin in tendon tissue remodeling after denervation-induced mechanical stress deprivation.
It has been shown that musculoskeletal tissues undergo dynamic tissue remodeling by a process that is quite sensitive to the mechanical environment. However, the detailed molecular mechanism underlying this process remains unclear. We demonstrate here that after denervation-induced mechanical stress deprivation, tendons undergo dynamic tissue remodeling as evidenced by a significant reduction of the collagen fibril diameter. Importantly, the transient up-regulation of osteopontin (OPN) expression was characteristic during the early phase of tendon tissue remodeling. Following this dynamic change of OPN expression, matrix metalloproteinase (MMP)-13 expression was induced, which presumably accounts for the morphological changes of tendon by degrading tendon collagen fibrils. The modulation of MMP-13 expression by OPN was specific, since the expression of MMP-2, which is also known to be involved in tissue remodeling, did not alter in the tendons under the absence or presence of OPN. We also demonstrate that the modulation of MMP-13 expression by OPN is due to the signaling through cell surface receptors for OPN. Thus, we conclude that OPN plays a crucial role in conveying the effect of denervation-induced mechanical stress deprivation to the tendon fibroblasts to degrade the extracellular matrices by regulating MMP-13 expression in tendon fibroblasts.
Mori
Noriaki
N
Department of Orthopaedic Surgery, Hokkaido University School of Medicine, Sapporo, Japan.
Majima
Tokifumi
T
Iwasaki
Norimasa
N
Kon
Shigeyuki
S
Miyakawa
Kiyoshi
K
Kimura
Chiemi
C
Tanaka
Kunio
K
Denhardt
David T
DT
Rittling
Susan
S
Minami
Akio
A
Uede
Toshimitsu
T
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism*; D003714:Denervation; D005109:Extracellular Matrix / Q000378:metabolism*; D005267:Femoral Nerve / Q000601:surgery; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D039302:Integrin alphaVbeta3 / Q000276:immunology; D007700:Kinetics; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009842:Oligopeptides / Q000494:pharmacology; D053495:Osteopontin / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D017847:Patellar Ligament / Q000294:innervation / Q000378:metabolism*; D013314:Stress, Mechanical
D000906:Antibodies; D039302:Integrin alphaVbeta3; D009842:Oligopeptides; C092614:glycyl-arginyl-glycyl-glutamyl-serine; D053495:Osteopontin; D003094:Collagen; C049554:glycyl-arginyl-glycyl-aspartyl-serine; D053509:Matrix Metalloproteinase 13