Human Achilles tendon mechanical behavior is more strongly related to collagen disorganization than advanced glycation end-products content

Diabetes is associated with impaired tendon homeostasis and subsequent tendon dysfunction, but the mechanisms underlying these associations is unclear. Advanced glycation end-products (AGEs) accumulate with diabetes and have been suggested to alter tendon function. In vivo imaging in humans has suggested collagen disorganization is more frequent in individuals with diabetes, which could also impair tendon mechanical function. The purpose of this study was to examine relationships between tendon tensile mechanics in human Achilles tendon with accumulation of advanced glycation end-products and collagen disorganization. Achilles tendon specimens (n = 16) were collected from individuals undergoing lower extremity amputation or from autopsy. Tendons were tensile tested with simultaneous quantitative polarized light imaging to assess collagen organization, after which AGEs content was assessed using a fluorescence assay. Moderate to strong relationships were observed between measures of collagen organization and tendon tensile mechanics (range of correlation coefficients: 0.570–0.727), whereas no statistically significant relationships were observed between AGEs content and mechanical parameters (range of correlation coefficients: 0.020–0.210). Results suggest that the relationship between AGEs content and tendon tensile mechanics may be masked by multifactorial collagen disorganization at larger length scales (i.e., the fascicle level).

RhoA within myofibers controls satellite cell microenvironment to allow hypertrophic growth

SummaryAdult skeletal muscle is a plastic tissue that can adapt its size to workload. Here, we show that RhoA within myofibers is needed for overload-induced hypertrophy by controlling satellite cell fusion to the growing myofibers without affecting protein synthesis. At the molecular level, we demonstrate that, in response to increased workload, RhoA controls in a cell autonomous manner Erk1/2 activation and the expressions of extracellular matrix (ECM) regulators such as Mmp9/Mmp13/Adam8 and of macrophage chemo-attractants such as Ccl3/Cx3cl1. Their decreased expression in RhoA mutant is associated with ECM and fibrillar collagen disorganization and lower macrophage infiltration. Moreover, Mmps inhibition and macrophage depletion in controls phenocopied the lack of growth of RhoA mutants. These findings unravel the implication of RhoA within myofibers, in response to increase load, in the building of a permissive microenvironment for muscle growth and for satellite cell accretion through ECM remodeling and inflammatory cell recruitment.

Bacterial cellulose and bacterial cellulose/polycaprolactone composite as tissue substitutes in rabbits' cornea

ABSTRACT: In order to test the performance of bacterial cellulose/polycaprolactone composite (BC/PCL) and pure bacterial cellulose (BC) as tissue substitutes in rabbits' cornea, a superficial ulcer containing 5mm in diameter and 0.2mm deep was made in the right cornea of 36 rabbits, then a interlayer pocket was created from the basis of this ulcer. Twelve rabbits received BC/PCL membrane and 12 were treated with BC membranes, both membranes with 8mm in diameter. The remaining rabbits received no membrane constituting the control group. The animals were clinically followed up for 45 days. Three animals of each group were euthanized at three, seven, 21, and 45 days after implantation for histological examination of the cornea along with the implant. Clinical observation revealed signs of moderate inflammatory process, decreasing from day 20th in the implanted groups. Histology showed absence of epithelium on the membranes, fibroplasia close to the implants, lymph inflammatory infiltrate with giant cells, collagen disorganization, with a predominance of immature collagen fibers in both groups with implants. Although inflammatory response is acceptable, the membranes used does not satisfactorily played the role of tissue substitute for the cornea during the study period.

ANALYSIS OF COLLAGEN PROFILE AND ORIENTATION IN A CHRONIC RUPTURED EXTENSOR POLLICIS LONGUS TENDON

Purpose: The purpose of this study is to examine the collagen profile and orientation in a ruptured extensor pollicis longus (EPL) tendon, in order to better understand the collagen response to loss of tensile forces. Methods: A 76-year-old male with a history of rheumatoid arthritis required surgical reconstruction of a chronic EPL rupture using EIP tendon transfer; the refreshed tip of the distal EPL tendon, along with the intervening tubular scar and EIP tendon were further analyzed. Picrosirus red (PSR) staining was performed, and the levels of collagen isoform were determined with western blotting. Results: The results obtained from PSR staining under polarized microscopy showed thin, weakly birefringent, green fibers (collagen III-like) and thick, yellow-red, strongly birefringent fibers (collagen I-like). The arrangement was noted to be much less organized and directional in the ruptured tendon compared to the EIP tendon. Western blotting results showed the presence of collagen I, II, III, V, VI and X, with the ratio comparison to collagen I markedly different between a normal EIP tendon and the ruptured EPL tendon. Conclusion: EPL tendon rupture is accompanied by collagen disorganization and significant alteration in the collagen isoform expression, postulated to be a consequence of the loss of tensile forces.

TENDINOSIS OF THE ROTATOR CUFF: A REVIEW

Rotator cuff tendinosis is a disease whose etiology and pathophysiology are still under debate. Three mechanisms have been proposed as giving rise to rotator cuff disease: the intrinsic mechanism, the extrinsic mechanism and overuse. Evidence for and against each one as being the primary cause of disease abounds. The current consensus is that the etiology is probably multifactorial and each factor plays different roles in different patients. The histologic features of rotator cuff disease are fibroblast hyperplasia, collagen disorganization and neovascularization. These findings together are termed angiofibroblastic hyperplasia, believed to be a reflection of unsuccessful attempts at repair of tendon with a tendency towards degeneration. The concept supports the current view that rotator cuff disease is a tendinosis, a degenerative process, rather than a tendinitis, an inflammatory one. This poor healing response is seen in the collagen content of diseased tendon. Production of collagen fails to shift from the initial type III collagen to the mature type I collagen, causing the tendon to become weak. Most current treatment modalities fail to address the biologic processes going on within the tendon and future directions need to address these problems.