ASGSB 2002 Annual Meeting Abstracts


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.

   Microgravity 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 no effect.

(Supported by NASA Grant: NAG9-1152)


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