The promoting effect of pentadecapeptide BPC 157 on tendon healing involves tendon outgrowth, cell survival, and cell migration

被引:96
作者
Chang, Chung-Hsun [1 ,2 ]
Tsai, Wen-Chung [3 ]
Lin, Miao-Sui [3 ]
Hsu, Ya-Hui [1 ]
Pang, Jong-Hwei Su [1 ]
机构
[1] Chang Gung Univ, Grad Inst Clin Med Sci, Tao Yuan 333, Taiwan
[2] Taipei Med Univ, Dept Orthopaed, Wan Fang Hosp, Taipei, Taiwan
[3] Chang Gung Univ, Dept Phys Med & Rehabil, Chang Gung Mem Hosp Linkou, Coll Med, Tao Yuan 333, Taiwan
关键词
BPC; 157; tendon healing; outgrowth; migration; FAK; paxillin; RAT ACHILLES-TENDON; GASTRIC PENTADECAPEPTIDE; PL; 14736; BPC-157; EXPRESSION; GRANULATION; LIGAMENT; THERAPY; STOMACH; LESIONS;
D O I
10.1152/japplphysiol.00945.2010
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Pentadecapeptide BPC 157, composed of 15 amino acids, is a partial sequence of body protection compound (BPC) that is discovered in and isolated from human gastric juice. Experimentally it has been demonstrated to accelerate the healing of many different wounds, including transected rat Achilles tendon. This study was designed to investigate the potential mechanism of BPC 157 to enhance healing of injured tendon. The outgrowth of tendon fibroblasts from tendon explants cultured with or without BPC 157 was examined. Results showed that BPC 157 significantly accelerated the outgrowth of tendon explants. Cell proliferation of cultured tendon fibroblasts derived from rat Achilles tendon was not directly affected by BPC 157 as evaluated by MTT assay. However, the survival of BPC 157-treated cells was significantly increased under the H2O2 stress. BPC 157 markedly increased the in vitro migration of tendon fibroblasts in a dose-dependent manner as revealed by transwell filter migration assay. BPC 157 also dose dependently accelerated the spreading of tendon fibroblasts on culture dishes. The F-actin formation as detected by FITC-phalloidin staining was induced in BPC 157-treated fibroblasts. The protein expression and activation of FAK and paxillin were determined by Western blot analysis, and the phosphorylation levels of both FAK and paxillin were dose dependently increased by BPC 157 while the total amounts of protein was unaltered. In conclusion, BPC 157 promotes the ex vivo outgrowth of tendon fibroblasts from tendon explants, cell survival under stress, and the in vitro migration of tendon fibroblasts, which is likely mediated by the activation of the FAK-paxillin pathway.
引用
收藏
页码:774 / 780
页数:7
相关论文
共 32 条
[1]   Serine phosphorylation regulates paxillin turnover during cell migration [J].
Zeid N.A. ;
Vallés A.-M. ;
Boyer B. .
Cell Communication and Signaling, 4 (1)
[2]   Enhanced tendon healing with GDF 5 and 6 [J].
Aspenberg, P ;
Forslund, C .
ACTA ORTHOPAEDICA SCANDINAVICA, 1999, 70 (01) :51-54
[3]  
Beason D.P., 2008, ORTHOPAEDIC KNOWLEDG, V9, P35
[4]   The stable gastric pentadecapeptide BPC 157, given locally, improves CO2 laser healing in mice [J].
Bilic, M ;
Bumber, Z ;
Blagaic, AB ;
Batelja, L ;
Seiwerth, S ;
Sikiric, P .
BURNS, 2005, 31 (03) :310-315
[5]   Evidence for direct cellular protective effect of PL-10 substances (synthesized parts of body protection compound, BPC) and their specificity to gastric mucosal cells [J].
Bodis, B ;
Karadi, O ;
Nemeth, P ;
Dohoczky, C ;
Kolega, M ;
Mozsik, G .
LIFE SCIENCES, 1997, 61 (16) :PL243-PL248
[6]  
Brcic L, 2009, J PHYSIOL PHARMACOL, V60, P191
[7]   FOCAL ADHESIONS - TRANSMEMBRANE JUNCTIONS BETWEEN THE EXTRACELLULAR-MATRIX AND THE CYTOSKELETON [J].
BURRIDGE, K ;
FATH, K ;
KELLY, T ;
NUCKOLLS, G ;
TURNER, C .
ANNUAL REVIEW OF CELL BIOLOGY, 1988, 4 :487-525
[8]   Pentadecapeptide BPC 157 (PL 14736) Improves Ligament Healing in the Rat [J].
Cerovecki, Tomislav ;
Bojanic, Ivan ;
Brcic, Luka ;
Radic, Bozo ;
Vukoja, Ivan ;
Seiwerth, Sven ;
Sikiric, Predrag .
JOURNAL OF ORTHOPAEDIC RESEARCH, 2010, 28 (09) :1155-1161
[9]  
DUVNJAK M, 1992, ACTA PHYSL HUNG, V80, P89
[10]   GENETIC EXPRESSION FOR TYPE-I PROCOLLAGEN IN THE EARLY STAGES OF FLEXOR TENDON HEALING [J].
GELBERMAN, RH ;
AMIEL, D ;
HARWOOD, F .
JOURNAL OF HAND SURGERY-AMERICAN VOLUME, 1992, 17A (03) :551-558