In this investigation it has been demonstrated that specific growth factors are able to modify collagen secretion in explants from healing rabbit medial collateral ligaments. The addition of 2.5 ng transforming growth factor beta 1 (TGF-beta 1)/mL to 3-week-old scar explants resulted in an increase in the total amount of collagen secreted. Analysis of collagen types I and III individually revealed that the increase mediated by TGF-beta 1 was due primarily to an increase in collagen type I secretion. This led to a ratio of type I:type III that is closer to that found in normal ligament tissue. The addition of 100 ng insulin-like growth factor 2 (IGF-2) to explant cultures of 3-week-old scar tissue also led to an increase in the quantity of collagen secreted, but the increase was in both type I and III collagens. These effects were observed to a lesser degree in 6-week-old scar tissue, and by 12 weeks postinjury, minimal effects of the growth factors on collagen synthesis was detected. Neither growth factor influenced collagen secretion by normal ligament or synovium. In contrast, IGF-1 (100 ng/mL) or basic fibroblast growth factor (bFGF) (10 ng/mL) did not exert a detectable effect on collagen secretion by any of the normal or healing tissues. These results indicate that TGF-beta 1 and IGF-2 can modify the metabolic activity of cells in explants of healing ligaments early after injury and may enhance the repair process leading to improved function.
Based on the heterogeneity of the rabbit medial collateral ligament (MCL) along its length, we tested the hypothesis that injury location would affect its healing response. The right MCL of 80 skeletally mature New Zealand white rabbits was sectioned adjacent to bone at the femoral end (40 rabbits) or the tibial end (40 rabbits) and reapposed with sutures. Animals were killed after 3, 6, 14, or 40 weeks of healing to examine wounds histologically (2 rabbits per healing interval) and mechanically (8 rabbits per healing interval). Results of the mechanical tests were compared to midsubstance MCL repairs (24 rabbits) and to uninjured normal MCLs (20 rabbits). The morphology of the near-insertion repairs was characterized by abnormal callus-like formation and patchy bone resorption, particularly at the tibial insertion. Mechanically, insertional injuries remodeled towards normal MCL low-load, viscoelastic and failure properties more slowly than midsubstance injuries at the early healing intervals. After 40 weeks of healing, few injury-specific differences persisted. All injured ligaments had ultimate strengths 15-35 percent short of normal at 40 weeks and the femorally-injured ligaments were weaker than normal at this time. These results suggest that rabbit MCLs, injured near either end, heal more slowly than those injured in their midsubstance and develop abnormal insertion morphology.
In this investigation we have demonstrated that specific growth factors are able to modify plasminogen activator (PA) activity in explants from both normal and healing ligaments. Specifically, the addition of insulin-like growth factor 2 (IGF-2; 100 ng/mL) and transforming growth factor beta 1 (TGF-beta 1; 2.5 ng/mL) to explants of unoperated and healing ligaments resulted in a decrease in both PA and PA--PA-binding protein complex in conditioned medium from several tissues, and particularly in medial collateral ligament (MCL) scar tissue. This effect was observed in the explants from 3-, 6-, and 12-week healing scar tissue. In addition, IGF-2 and TGF-beta 1 influenced PA release from MCL tissue derived from the unoperated knee joint of 3-week healing animals. In contrast, basic fibroblast growth factor (b-FGF; 10 ng/mL) and IGF-1 (100 ng/mL) did not cause a detectable alteration of PA and PA--PA-binding protein complex activity in any of the healing or unoperated ligaments analyzed. These results indicate that specific growth factors are able to modify the activity of cells in explants of ligament and healing ligament in a distinct manner.
Mature bone can adapt to strenuous exercise, but no study has correlated the changes in bone in vivo strains, remodelling and mechanical properties that occur as a consequence of strenuous training. Therefore, we examined exercise-related remodelling and in vivo strains in the tarsometatarsus (TMT) of three groups of adult (post-physial closure) White Leghorn roosters: basal control (30 weeks of age), age-matched control (39 weeks) and exercise (39 weeks). Exercise birds ran for 1 h a day, 5 days a week for 9 weeks at 70–75% of predicted maximum aerobic capacity. During treadmill locomotion, in vivo strains were recorded from miniature rosette strain gauges implanted on anterior, medial and lateral TMT cortices. TMT mechanical properties were measured with three-point bending tests to failure. Cortical morphometry was digitized from photographic slides of a 1-mm thick mid-diaphysial cross section of each bone. Exercise and age-matched control TMTs had significantly greater cortical area and maximum load than had basal controls. Exercise axial strains significantly exceeded basal and age-matched control strains along the anterior and lateral surfaces. Age-matched control anterior axial strain was twice that of the basal control. The mature bone remodelling suggested that the structural properties optimized by exercise-induced remodelling may differ from those optimized by age-related remodelling. The findings support the osteoregulatory role of strain but contradict earlier data suggesting that strain magnitudes do not change significantly with age or exercise.
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