ACUTE WOUND HEALING AND REPAIR OF RODENT MCL DURING
HINDLIMB UNWEIGHTING IN RESPONSE TO RHGH AND IGF-I. COUNTERMEASURES.
D.A. Martinez1, R. Vanderby, Jr.2, R.E. Grindeland3,
A.K. Lee1, H.Y. Hoang1, P. Le1, A. Lust1, N.
Garcia1 and A.C. Vailas1. 1Connective Tissue
Physiol. Lab, Univ. of Houston, TX, 2Dept. of Surgery, Univ. of
Wisconsin, Madison, WI, 3NASA-Ames, Moffett Field, CA.
and simulated microgravity have pronounced detrimental effects on the strength
and composition of dense fibrous connective tissues. Previously we have reported
that the time course of wound healing in the rodent medial collateral ligament (MCL)
during hindlimb unweighting (HLS) is significantly delayed, which was
demonstrated by reduced ligament strength and stiffness, decreased ECM
organization , elevated MCL cellularity, altered collagen characteristics. rhGH
and IGF-I are known to be potent anabolic endocrine modulators of collagen
metabolism. Therefore, our primary purpose of this study was to use rhGH, IGF-I
and rhGH+IGF-I as countermeasure therapies to ameliorate the “delayed”
injury repair response of the MCL during HLS. Ten rats in each group were
randomly assigned to HLS or ambulatory (AMB) groups receiving either bilateral
MCL lesions or sham surgeries. Each group and their respective controls received
twice daily injections (s.c.) of rhGH, rhIGF-I, rhGH+IGF-I or saline for 3
weeks. MCL biochemical analyses showed an increase in DNA concentration (P<0.05)
in lesion MCL’s that were partially restored by IGF-I. There was an increase
in proteoglycans in the lesion groups, however there was no effect by hormone
countermeasures (P>0.05). MCL hydroxyproline (Hyp) concentration was
reduced in both the lesion and unweighted groups. rhGH or IGF-I supplementation
did not alter MCL collagen concentrations. The maturation of the MCL collagen
measured by the content of HP cross-links showed that unweighting by itself
increased HP cross-link content, while rats exposed to both surgical lesions and
unweighting had greater HP contents indicative of mature un-remodeled collagen.
rhGH treatment increased MCL HP content in HLS+lesion animals, whereas IGF-I had
(Supported by NASA Grant: NAG9-1152)