Temporal extracellular matrix adaptations in ligament during wound healing and hindlimb unloading

Abstract

Martinez DA, Vailas AC, Vanderby R Jr, Grindeland RE. Temporal extracellular matrix adaptations in ligament during wound healing and hindlimb unloading. Am J Physiol Regul Integr Comp Physiol 293: R1552-R1560, 2007. First published August 15, 2007 doi:10.1152/ajpregu.00423.2007.-Previous data from spaceflight studies indicate that injured muscle and bone heal slowly and abnormally compared with ground controls, strongly suggesting that ligaments or tendons may not repair optimally as well. Thus the objective of this study was to investigate the biochemical and molecular gene expression of the collagen extracellular matrix in response to medial collateral ligament (MCL) injury repair in hindlimb unloaded (HLU) rodents. Male rats were assigned to 3-and 7-wk treatment groups with three subgroups each: sham control, ambulatory healing (Amb-healing), and HLU-healing groups. Amb-and HLU-healing animals underwent bilateral surgical transection of their MCLs, whereas control animals were subjected to sham surgeries. All surgeries were performed under isoflurane anesthesia. After 3 wk or 7 wk of HLU, rats were euthanized and MCLs were surgically isolated and prepared for molecular or biochemical analyses. Hydroxyproline concentration and hydroxylysylpyridinoline collagen cross-link contents were measured by HPLC and showed a substantial decrement in surgical groups. MCL tissue cellularity, quantified by DNA content, remained significantly elevated in all HLU-healing groups vs. Amb-healing groups. MCL gene expression of collagen type I, collagen type III, collagen type V, fibronectin, decorin, biglycan, lysyl oxidase, matrix metalloproteinase-2, and tissue inhibitor of matrix metalloproteinase-1, measured by real-time quantitative PCR, demonstrated differential expression in the HLU-healing groups compared with Ambhealing groups at both the 3-and 7-wk time points. Together, these data suggest that HLU affects dense fibrous connective tissue wound healing and confirms previous morphological and biomechanical data that HLU inhibits the ligament repair processes.

Patterns of Gene Expression in a Rabbit Partial Anterior Cruciate Ligament Transection Model

“…The MCL injury models have shown a similar increase in Col I and III expression for up to 12 weeks postoperatively. 29,33 A study using rat tendon fascicles found that application of cyclic strain over a 24-hour period increased the production and retention of newly synthesized collagen fascicles in comparison with shorter durations, which inhibited collagen synthesis. 31 Vol.…”

Functional management of ankle sprains: what volume and intensity of walking is undertaken in the first week postinjury

“…There is evidence from animal models that mechanically loading injured soft tissue prompts a range of cellular responses that promote tissue structural change and recovery 11. These responses include an upregulation of mRNA expression for key proteins associated with soft tissue healing,12–14 and enhanced strength and morphological characteristics of collagenous tissue 12 13…”

An in Vitro Study on Tissue Repair: Impact of Unloading on Cells Involved in the Remodelling Phase

“…Research performed on rats revealed bone healing impairment, with reduced callus formation and reduced angiogenesis (Midura et al 2006), disruptions in the microvasculature of injured muscles, with delayed muscle repair processes (Heinemeier et al 2009), reduced ECM deposition in tendons and ligaments, with corresponding decrease in strength and alteration of repair mechanisms in connective tissues (Provenzano et al 2003;Martinez et al 2007). Moreover, impaired angiogenesis has been reported (Radek et al 2008).…”