Expression of insulin-like growth factor I, insulin-like growth factor binding proteins, and collagen mRNA in mechanically loaded plantaris tendon.
Insulin-like growth factor I (IGF-I) is known to exert an anabolic effect on tendon fibroblast production of collagen. IGF-I's regulation is complex and involves six different IGF binding proteins (IGFBPs). Of these, IGFBP-4 and -5 could potentially influence the effect of IGF-I in the tendon because they both are produced in fibroblast; however, the response of IGFBP-4 and -5 to mechanical loading and their role in IGF-I regulation in tendinous tissue are unknown. A splice variant of IGF-I, mechano-growth factor (MGF) is upregulated and known to be important for adaptation in loaded muscle. However, it is not known whether MGF is expressed and upregulated in mechanically loaded tendon. This study examined the effect of mechanical load on tendon collagen mRNA in relation to changes in the IGF-I systems mRNA expression. Data were collected at 2, 4, 8 and 16 days after surgical removal of synergistic muscle to the plantaris muscle of the rat, thus increasing the load to plantaris muscle and tendon. Nearly a doubling of the tendon mass was observed after 16 days of loading. A rapid rise in tendon procollagen III mRNA was seen after 2 days whereas the increase in procollagen I mRNA was significant from day 8. MGF was expressed and upregulated in loaded tendon tissue with a faster response than IGF-I, which was increased from day 8. Finally, IGFBP-4 mRNA was increased with a time pattern similar to procollagen III, whereas IGFBP-5 decreased at day 8. In conclusion, loading of tendon tissue results in an upregulation of IGF-I, IGFBP-4, and procollagen and is associated with an increase in tendon mass. Also, MGF is expressed with an early upregulation in loaded tendon tissue. We suggest that the IGF-I system could be involved in collagen synthesis in tendon in response to mechanical loading.
Olesen
Jens L
JL
Institute of Sports Medicine, Bispebjerg Hospital, DK-2400 Copenhagen, Denmark. olesenjens@yahoo.dk
Heinemeier
Katja M
KM
Haddad
Fadia
F
Langberg
Henning
H
Flyvbjerg
Allan
A
Kjaer
Michael
M
Baldwin
Kenneth M
KM
D000818:Animals; D001696:Biomechanical Phenomena; D003094:Collagen / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D018974:Insulin-Like Growth Factor Binding Protein 4 / Q000378:metabolism; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000378:metabolism; D018969:Insulin-Like Growth Factor Binding Proteins / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000737:chemistry* / Q000502:physiology; D011347:Procollagen / Q000378:metabolism; D020033:Protein Isoforms / Q000032:analysis / Q000235:genetics / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis* / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013710:Tendons / Q000033:anatomy & histology / Q000737:chemistry* / Q000502:physiology*; D013997:Time Factors; D015854:Up-Regulation; D016474:Weight-Bearing
D018974:Insulin-Like Growth Factor Binding Protein 4; D018975:Insulin-Like Growth Factor Binding Protein 5; D018969:Insulin-Like Growth Factor Binding Proteins; D011347:Procollagen; D020033:Protein Isoforms; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D003094:Collagen