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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2005-8-15
pubmed:abstractText
In this study, we examined pathophysiological roles of osteoactivin, a functionally unknown type I membrane glycoprotein, in mouse skeletal muscle atrophied by denervation (sciatic neurectomy). Denervation increased the amounts of osteoactivin, vimentin, matrix metalloproteinase-3 (MMP-3), and MMP-9 in mouse gastrocnemius muscle. Interestingly, immunohistochemical analysis revealed that vimentin, MMP-3, and MMP-9 were mainly present in fibroblast-like cells infiltrated into denervated mouse gastrocnemius muscle, whereas osteoactivin was expressed in the sarcolemma of myofibers adjacent to the fibroblast-like cells. On the basis of these findings, we reasoned that osteoactivin in myocytes was involved in activation of the infiltrated fibroblasts. To address this issue, we examined effects of osteoactivin on expression of MMPs in fibroblasts in vitro and in vivo. Overexpression of osteoactivin in NIH-3T3 fibroblasts induced expression of MMP-3, but not in mouse C(2)C(12) myoblasts, indicating that osteoactivin might functionally target fibroblasts. Treatment with recombinant mouse osteoactivin increased the amounts of collagen type I, MMP-3, and MMP-9 in mouse NIH-3T3 fibroblasts. The upregulated expression of these fibroblast marker proteins was significantly inhibited by heparin, but not by an integrin inhibitor, indicating that a heparin-binding motif in the extracellular domain might be an active site of osteoactivin. In osteoactivin-transgenic mice, denervation further enhanced expression of MMP-3 and MMP-9 in fibroblasts infiltrated into gastrocnemius muscle, compared with wild-type mice. Our present results suggest that osteoactivin might function as an activator for fibroblasts infiltrated into denervated skeletal muscles and play an important role in regulating degeneration/regeneration of extracellular matrix.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0363-6143
pubmed:author
pubmed:issnType
Print
pubmed:volume
289
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
C697-707
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:16100390-Animals, pubmed-meshheading:16100390-Cells, Cultured, pubmed-meshheading:16100390-Collagen Type I, pubmed-meshheading:16100390-Fibroblast Growth Factor 2, pubmed-meshheading:16100390-Fibroblasts, pubmed-meshheading:16100390-Gene Expression, pubmed-meshheading:16100390-Hindlimb, pubmed-meshheading:16100390-Male, pubmed-meshheading:16100390-Matrix Metalloproteinase 3, pubmed-meshheading:16100390-Matrix Metalloproteinase 9, pubmed-meshheading:16100390-Membrane Glycoproteins, pubmed-meshheading:16100390-Mice, pubmed-meshheading:16100390-Mice, Inbred C57BL, pubmed-meshheading:16100390-Mice, Inbred DBA, pubmed-meshheading:16100390-Mice, Transgenic, pubmed-meshheading:16100390-Muscle, Skeletal, pubmed-meshheading:16100390-Muscle Denervation, pubmed-meshheading:16100390-Muscular Atrophy, pubmed-meshheading:16100390-Myoblasts, Skeletal, pubmed-meshheading:16100390-NIH 3T3 Cells, pubmed-meshheading:16100390-Platelet-Derived Growth Factor, pubmed-meshheading:16100390-Regeneration, pubmed-meshheading:16100390-Schwann Cells, pubmed-meshheading:16100390-Up-Regulation
pubmed:year
2005
pubmed:articleTitle
Osteoactivin upregulates expression of MMP-3 and MMP-9 in fibroblasts infiltrated into denervated skeletal muscle in mice.
pubmed:affiliation
Dept. of Orthopaedics, The University of Tokushima School of Medicine, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't