Connective Tissue Elasticity Research Articles

Improvement in the range of joint motion in seven patients with mucopolysaccharidosis type II during experimental gene expression‐targeted isoflavone therapy (GET IT)

Mucopolysaccharidosis type II (MPS II, Hunter disease) is an X chromosome-linked inherited metabolic disease caused by mutations resulting in deficiency of activity of iduronate-2-sulfatase (IDS) and accumulation of undegraded glycosaminoglycans (GAGs), heparan sulfate, and dermatan sulfate. Previous experiments with cell cultures and studies on animal model of MPS II suggested that gene expression-targeted isoflavone therapy (GET IT), based on genistein-mediated reduction of efficiency of GAG synthesis, might be a suitable therapy for this disease. In this report, we demonstrate efficacy of GET IT in connective tissue elasticity, particularly in improving the range of joint motion in seven patients with MPS II after 26 weeks of treatment with an isoflavone extract at the dose corresponding to 5 mg/kg/day of genistein.

Microanatomical structure of the human sciatic nerve

Sciatic nerve is the largest peripheral nerve of the human body. It gives motor and sensitive innervation for the most of lower limb. The aim of the present investigation was revealing his fascicular pattern in relation to microanatomic morphometric characteristics of its connective tissue sheaths. The material consisted of sciatic nerve slices, excised from 17 cadavers of humans aging 8-93 years. After routine histologic processing and light microscopic examination of the preparations, morphometric analysis was performed at magnifications of 40 and 630x. Sciatic nerve showed to be polyfascicular nerve type, with the group pattern of nerve fascicless distribution. The number of fascicless ranged from 27 to 70, whereas the number of fascicless per square millimeter was 1-4. Morphometric and correlation analysis confirmed the significant increase of whole sciatic nerve cross section area, which was associated with the significant increase of its epi- and perineural connective tissue sheaths. Interfascicular sciatic nerve domains of elderly persons contained more adipose tissue. Moreover, already detected loss and degeneration of the large myelinated nerve fibers within fascicles was accompanied by the significant increase of endoneural connective tissue. In conclusion, our study revealed comparative connective tissue enlargement of human sciatic nerve in the course of aging. These phenomena might influence on result of injured nerve's surgical reparations. We interpret this finding as non-specific compensatory phenomenon elicited by loss of thickest myelinated nerve fibers, higher vulnerability of remaining ones, and age-dependent decrease of connective tissue elasticity.

Characterisation of matrix metalloproteinase cleavage sites in fibrillin

Fibrillin is the principal structural component of the beaded elastic microfibrils of extracellular matrix (Keene et al. 1991; Kielty & Shuttleworth 1995). Fibrillins are ˜350 kD multidomain glycoproteins with repeating calcium binding epidermal growth factor-like domains interspersed with TB modules (Pereira et al. 1993). Loss of connective tissue elasticity in ageing and disease states may be a result of progressive damage to microfibrils. The matrix metalloproteinases (MMPs) are crucially important in degradation of connective tissue components in tissue development, wound healing, angiogenesis, tumour invasion and metastasis (Parks & Mecham 1993). We have identified 3 major MMP cleavage sites within fibrillin molecules.

THERAPEUTIC MODALITIES

Therapeutic modalities are commonly utilized in the treatment of athletic injuries. Modalities are reported to work via various peripheral and central mechanisms to control and override afferent pain signals. Topical cold therapy has been found to decrease blood flow, inhibit circulation of inflammatory mediators and to slow conduction of pain stimuli by peripheral nerves. Topical heat increases blood flow, increases elasticity of connective tissue, inhibits nociception and decreases central pain perception. Electrical stimulation causes muscle contraction, decreasing pain afferents and allowing for removal of metabolic byproducts. Iontophoresis and phonophoresis utilize electrical current and sound waves respectively to drive various medications through the skin. At the present time, the physiologic effects of modalities are incompletely understood leading to confusion as to when or why a particular modality should be utilized. Old paradigms regarding indications need to be re-examined in light of recent research findings. Newer strategies, such as continuous low level cryo- and thermtherapy may have superior therapeutic potential. Additionally, complications from modalities are poorly documented, though they are known to occur in a substantial number of patients. Overall, the general knowledge regarding therapeutic modalities is outdated with clinical texts lagging years behind current research.

Keratinocytes Influence the Maturation and Organization of the Elastin Network in a Skin Equivalent

Elastic fibers form a complex network that contributes to the elasticity of connective tissues. Alterations in the elastic fiber network are involved in several disease affecting organs in which compliance of the connective tissue is essential: skin, main vasculature, lung, joints, muscle, and ligament. The aim of our work was to study the deposition, maturation, and organization of elastic fiber components in a dermal equivalent model consisting of collagen-GAG-chitosan seeded with fibroblasts. The influence of keratinocytes was studied in parallel, thus constituting a skin equivalent model. These models were examined by transmission electron microscopy (TEM) and by immunohistochemistry to determine the staining patterns of fibrillin-1 and elastin proteins representative of the microfibrillar framework and of the elastic fibers, respectively. After 2 mo of fibroblast culture in the dermal equivalent, elastin was undetectable, whereas fibrillin-1 staining was weak and microfibrils were infrequently observed by TEM. In the skin equivalent, fibrillin-1 and elastin were detected by immunostaining 15 d after epidermization and TEM revealed the typical structure and organization of the elastic network in the dermis, with elastin deposition on the microfibrillar scaffold. This in vitro skin equivalent model is to our knowledge the first in which elastic fibers have been detected, thus demonstrating the influence of keratinocytes on the maturation and organization of the elastic network.

Fibrillin degradation by matrix metalloproteinases: implications for connective tissue remodelling

Fibrillin is the principal structural component of the 10-12 nm diameter elastic microfibrils of the extracellular matrix. We have previously shown that both fibrillin molecules and assembled microfibrils are susceptible to degradation by serine proteases. In this study, we have investigated the potential catabolic effects of six matrix metalloproteinases (MMP-2, MMP-3, MMP-9, MMP-12, MMP-13 and MMP-14) on fibrillin molecules and on intact fibrillin-rich microfibrils isolated from ciliary zonules. Using newly synthesized recombinant fibrillin molecules, major cleavage sites within fibrillin-1 were identified. In particular, the six different MMPs generated a major degradation product of approximately 45 kDa from the N-terminal region of the molecule, whereas treatment of truncated, unprocessed and furin-processed C-termini also generated large degradation products. Introduction of a single ectopia lentis-causing amino acid substitution (E2447K; one-letter symbols for amino acids) in a calcium-binding epidermal growth factor-like domain, predicted to disrupt calcium binding, markedly altered the pattern of C-terminal fibrillin-1 degradation. However, the fragmentation pattern of a mutant fibrillin-1 with a comparable E-->K substitution in an upstream calcium-binding epidermal growth factor-like domain was indistinguishable from wild-type molecules. Ultrastructural examination highlighted that fibrillin-rich microfibrils isolated from ciliary zonules were grossly disrupted by MMPs. This is the first demonstration that fibrillin molecules and fibrillin-rich microfibrils are degraded by MMPs and that certain amino acid substitutions change the fragmentation patterns. These studies have important implications for physiological and pathological fibrillin catabolism and for loss of connective tissue elasticity in ageing and disease.

Fibrillin degradation by matrix metalloproteinases: implications for connective tissue remodelling

Fibrillin is the principal structural component of the 10-12 nm diameter elastic microfibrils of the extracellular matrix. We have previously shown that both fibrillin molecules and assembled microfibrils are susceptible to degradation by serine proteases. In this study, we have investigated the potential catabolic effects of six matrix metalloproteinases (MMP-2, MMP-3, MMP-9, MMP-12, MMP-13 and MMP-14) on fibrillin molecules and on intact fibrillin-rich microfibrils isolated from ciliary zonules. Using newly synthesized recombinant fibrillin molecules, major cleavage sites within fibrillin-1 were identified. In particular, the six different MMPs generated a major degradation product of ~ 45 kDa from the N-terminal region of the molecule, whereas treatment of truncated, unprocessed and furin-processed C-termini also generated large degradation products. Introduction of a single ectopia lentis-causing amino acid substitution (E2447K; one-letter symbols for amino acids) in a calcium-binding epidermal growth factor-like domain, predicted to disrupt calcium binding, markedly altered the pattern of C-terminal fibrillin-1 degradation. However, the fragmentation pattern of a mutant fibrillin-1 with a comparable E → K substitution in an upstream calcium-binding epidermal growth factor-like domain was indistinguishable from wild-type molecules. Ultrastructural examination highlighted that fibrillin-rich microfibrils isolated from ciliary zonules were grossly disrupted by MMPs. This is the first demonstration that fibrillin molecules and fibrillin-rich microfibrils are degraded by MMPs and that certain amino acid substitutions change the fragmentation patterns. These studies have important implications for physiological and pathological fibrillin catabolism and for loss of connective tissue elasticity in ageing and disease.

Musculoskeletal injury in the older athlete

AbstractThe number of athletes over the age of 50 is increasing and the future will likely see a greater demand for means of prolonging their careers. The purpose of this review was to investigate injury prevention in older athletes by examining age-related musculoskeletal changes, the nature of sports injuries in aged people, and injury prevention methods in the general athletic population. Results have indicated that ageing leads to decreased bone density, connective tissue elasticity, and muscle mass, volume and strength. Many of these changes may be reversible to some degree with exercise. Older athletes most commonly suffer chronic overuse injuries of the knee and shoulder. Injury prevention involves minimizing the intrinsic and extrinsic risk factors specific to the individual. In conclusion, it seems reasonable that modified injury prevention methods would be effective for the older athlete. A prevention model specific to older athletes is provided.

Toward a kinetic theory of connective tissue micromechanics.

The aim of this study is to develop unifying concepts at the microstructural level to account for macroscopic connective tissue dynamics. We establish the hypothesis that rate-dependent and rate-independent dissipative stresses arise in the interaction among fibers in the connective tissue matrix. A quantitative theoretical analysis is specified in terms of geometry and material properties of connective tissue fibers and surrounding constituents. The analysis leads to the notion of slip and diffusion boundary layers, which become unifying concepts in understanding mechanisms that underlie connective tissue elasticity and energy dissipation during various types of loading. The complex three-dimensional fiber network is simplified to the interaction of two ideally elastic fibers that dissipate energy on slipping interface surfaces. The effects of such interactions are assumed to be expressed in the aggregate matrix. Special solutions of the field equations are obtained analytically, whereas the general solution of the model field equations is obtained numerically. The solutions lead to predictions of tissue behavior that are qualitatively, if not quantitatively, consistent with reports of a variety of dynamic moduli, their dependencies on the rate and amplitude of load application, and some features associated with preconditioning.

Collagen distribution in the lamina cribrosa and the trabecular meshwork of the human eye.

Tengroth and Ammitzböll found the collagen content of the optic disc in glaucoma to differ from that of normal eyes. A theory was advanced that a primary collagen disturbance might be involved in the pathogenesis of glaucoma. The connective tissue in the body has a supportive function in almost all the organs. The tensile strength and elasticity of connective tissue is mainly due to the presence of collagen fibres and elastic fibres, which also maintain the shape of the tissues. There are many different types of collagen, three of which are discussed in this paper. Type I collagen is found in tendons, skin, and numerous other organs, for example the eye. Type III is found mainly in the blood vessels but is also present in other tissues with a mesodermal origin, and type IV is found in the basement membranes. To elucidate the precise distribution of collagen types in the ocular structures an immunhistochemical study was undertaken in normal human eyes. The amino acids proline, hydroxyproline, and hydroxylysine, which are characteristic of collagen, were also analysed. Collagen types I, III, and IV were found in the lamina cribrosa, the trabecular meshwork, and the retrolaminary optic nerve. In contrast, only type I was found in the sclera.