PMID- 16100390
OWN - NLM
STAT- MEDLINE
DCOM- 20050923
LR  - 20200930
IS  - 0363-6143 (Print)
IS  - 0363-6143 (Linking)
VI  - 289
IP  - 3
DP  - 2005 Sep
TI  - Osteoactivin upregulates expression of MMP-3 and MMP-9 in fibroblasts infiltrated 
      into denervated skeletal muscle in mice.
PG  - C697-707
AB  - 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.
FAU - Ogawa, Takayuki
AU  - Ogawa T
AD  - Dept. of Orthopaedics, The University of Tokushima School of Medicine, 3-18-15 
      Kuramoto-cho, Tokushima 770-8503, Japan.
FAU - Nikawa, Takeshi
AU  - Nikawa T
FAU - Furochi, Harumi
AU  - Furochi H
FAU - Kosyoji, Miki
AU  - Kosyoji M
FAU - Hirasaka, Katsuya
AU  - Hirasaka K
FAU - Suzue, Naoto
AU  - Suzue N
FAU - Sairyo, Koichi
AU  - Sairyo K
FAU - Nakano, Shunji
AU  - Nakano S
FAU - Yamaoka, Takashi
AU  - Yamaoka T
FAU - Itakura, Mitsuo
AU  - Itakura M
FAU - Kishi, Kyoichi
AU  - Kishi K
FAU - Yasui, Natsuo
AU  - Yasui N
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Physiol Cell Physiol
JT  - American journal of physiology. Cell physiology
JID - 100901225
RN  - 0 (Collagen Type I)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Platelet-Derived Growth Factor)
RN  - 103107-01-3 (Fibroblast Growth Factor 2)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Collagen Type I/metabolism
MH  - Fibroblast Growth Factor 2/pharmacology
MH  - Fibroblasts/enzymology
MH  - Gene Expression/physiology
MH  - Hindlimb
MH  - Male
MH  - Matrix Metalloproteinase 3/genetics/*metabolism
MH  - Matrix Metalloproteinase 9/genetics/*metabolism
MH  - Membrane Glycoproteins/genetics/*metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Inbred DBA
MH  - Mice, Transgenic
MH  - *Muscle Denervation
MH  - Muscle, Skeletal/innervation/pathology/*physiology
MH  - Muscular Atrophy/metabolism/pathology
MH  - Myoblasts, Skeletal/cytology/drug effects
MH  - NIH 3T3 Cells
MH  - Platelet-Derived Growth Factor/pharmacology
MH  - Regeneration/physiology
MH  - Schwann Cells/cytology/enzymology
MH  - Up-Regulation
EDAT- 2005/08/16 09:00
MHDA- 2005/09/24 09:00
CRDT- 2005/08/16 09:00
PHST- 2005/08/16 09:00 [pubmed]
PHST- 2005/09/24 09:00 [medline]
PHST- 2005/08/16 09:00 [entrez]
AID - 289/3/C697 [pii]
AID - 10.1152/ajpcell.00565.2004 [doi]
PST - ppublish
SO  - Am J Physiol Cell Physiol. 2005 Sep;289(3):C697-707. doi: 
      10.1152/ajpcell.00565.2004.