elastin and Intervertebral-Disc-Degeneration

The aim of the study was to assess the relationship between the expression of elastin, collagen type I, II,III and the degenera- tion of the facet joint capsule and the ligamentum flavum.. 10 patients (4 male, 6 female) (mean age 61 ± 14,9) undergoing surgery for degenerative lumbar spine syndrome and 5 cadav- ers (3 male, 2 female) (age of death 87 ± 8,6 years) were included in this study. One set of tissue samples was taken from each patient in the patient group intraoperatively and two sets of samples were taken from each cadaver in the cadaver group posthumosly from the ligamentum flavum (medial and lateral) and from the facet joint capsules (superior and inferior articular process) at the L4/5 segment. Western blot analysis was performed for collagen types I, II, III and for elastin. Disc degeneration was scored according to the Pfirmann Classification, facet joint arthrosis was scored according to the Fujiwara Classification and their relationship with protein expression was investigated.. There was a strong expression of Collagen type I in the patient group (PG) compared to the body donor group (BDG) in the facet joint capsule (FJC) and in the lateral samples of the ligamentum flavum. Samples of the FJC showed lower expression of elastin in the PG compared with the BDG, but without statistical significance. An increased expression of collagen type I compared to elastin in the PG could be shown. In contrast, elastin predominated in the samples of the BDG group compared to collagen type I (collagen type I/ elastin PG: PAsup 2,78; PAinf 2,61; LFmed 2,23; 225 LFlat 1,83; BDG: PAsup 0,15; PAinf 0,2; LFmed 0,2; LFlat 0,27). Rank correlation coefficient according to Spearman showed low to moderate correlations for collagen type I, III and elastin for the degree of disc degeneration accord- ing to Pfirrmann and the degree of facet joint osteoarthritis according to Fujiwara, all of them without statistical significance.. This study has shown us that in the context of degenerative changes of the lumbar spine, there is an increased expression of collagen type I and a dominance over elastin.. Level III, Diagnostic Study.

Topics: Aged, 80 and over; Cadaver; Collagen; Collagen Type I; Elastin; Female; Humans; Intervertebral Disc Degeneration; Joint Capsule; Ligamentum Flavum; Lumbar Vertebrae; Male; Middle Aged; Zygapophyseal Joint

Aging and degeneration of human intervertebral disc (IVD) are associated with biochemical changes, including racemization and glycation. These changes can only be counteracted by protein turnover. Little is known about the longevity of IVD elastin in health or disease. Yet, such knowledge is important for a quantitative understanding of tissue synthesis and degradation.. We have measured the accumulation of d-Asp and pentosidine in IVD elastin. Samples representing a broad range of ages (28-82years) and degeneration grades (1-5) were analyzed.. d/l-Asp for elastin increased linearly with age from 3.2% (early 30s) to 14.8% (early 80s) for normal tissue (grades 1-2) and from 1.7% (late 20s) to 6.0% (until the mid 50s) for degenerate tissue (grades 3-5) with accumulation rates of 16.2±3.1×10(-4) and 11.7±3.8×10(-4)year(-1), respectively; no significant difference was found between these values (p<0.05). Above the mid 50s, a decrease in d-Asp accumulation was recorded in the degenerate tissue. d-Asp accumulation correlated well with pentosidine content for elastin from healthy and degenerate tissues combined. We conclude that IVD elastin is metabolically-stable and long-lived in both healthy and degenerate human IVDs, with signs of new synthesis in the latter. The correlation of d-Asp with pentosidine content suggests that both these agents may be used as markers in the overall aging process of IVD.. Accumulation of modified IVD elastin argues for its longevity and may have a negative impact on its role in disc function. Weak signs of newly synthesized molecules may act to counteract this effect in degenerate tissue.

Topics: Adult; Aged; Aged, 80 and over; Aging; Amino Acid Isomerases; Aspartic Acid; Autopsy; Elastin; Female; Humans; Intervertebral Disc; Intervertebral Disc Degeneration; Longevity; Male; Middle Aged; Molecular Probe Techniques; Time Factors

An in vitro biomechanical and imaging study generated from an in vivo porcine model of early stage degenerative disc disease was used to evaluate mechanical property restoration, comparing 2 minimally invasive injection techniques.. To evaluate the ability of an injectable hydrogel to restore the mechanical properties of spinal motion segments with early stage disc degeneration, comparing 2 minimally invasive injection techniques.. Treatment of early-stage disc degeneration may benefit from a combination of tissue engineering and minimally invasive therapeutic approaches. A recently developed hydrogel, thiol-modified hyaluronan elastin-like polypeptide (TMHA/EP) composite, has demonstrated potential as an injectable nucleus replacement.. From a total of thirteen 35-kg Yorkshire boars, early-stage lumbar disc degeneration was introduced into 10 pigs via injection of chondroitinase ABC. After degeneration, 8 pigs received TMHA/EP augmentation; 1 disc via direct needle injection and a second using a modified kyphoplasty approach. High-resolution magnetic resonance images were acquired of the excised spinal motion segments, followed by biomechanical testing in axial compression, flexion-extension, lateral bending, and torsion.. The degenerate control motion segments were generally less stiff and more flexible than healthy controls. The injection of TMHA/EP into the degenerated nucleus produced similar mechanical stiffness to healthy controls. The direct-injected discs showed a dispersive pattern of TMHA/EP within the nucleus, whereas the modified kyphoplasty method yielded a bolus of hydrogel. Yet, mechanical behavior was comparable considering the 2 minimally invasive augmentation techniques.. The TMHA/EP composite can restore initial mechanical behavior in early-stage disc degeneration. Although both augmentation methods yielded mechanical properties comparable with healthy controls, direct injection represents a simpler technique, uses a smaller-gauge needle, does not introduce air into the disc, and yields a dispersive pattern that may be beneficial for future delivery of cells or growth factors.

Topics: Animals; Biomechanical Phenomena; Disease Models, Animal; Elastin; Humans; Hyaluronic Acid; Hydrogel, Polyethylene Glycol Dimethacrylate; Intervertebral Disc; Intervertebral Disc Degeneration; Lumbar Vertebrae; Minimally Invasive Surgical Procedures; Peptides; Range of Motion, Articular; Sulfhydryl Compounds; Swine; Time Factors; Tissue Engineering; Total Disc Replacement; Treatment Outcome; Viscosupplements

Biomechanical, in vitro, and initial in vivo evaluation of a thiol-modified hyaluronan (TM-HA) and elastin-like polypeptide (ELP) composite hydrogel for nucleus pulposus (NP) tissue engineering.. To investigate the utility of a TM-HA and ELP composite material as a potential tissue-engineering scaffold to reconstitute the NP in early degenerative disc disease (DDD) on the basis of both biomechanical and biologic parameters.. DDD is a common ailment with enormous medical, psychosocial, and economic ramifications. Only end-stage surgical therapies are currently widely available. A less invasive, early stage therapy may provide a clinically relevant treatment option.. TM-HA and ELP were combined in various concentrations and cross-linked using poly (ethylene glycol) diacrylate. Resulting materials were evaluated biomechanically using confined compression to determine biphasic material properties. In vitro cell culture with human intervertebral disc (IVD) cells seeded within TM-HA/ELP scaffolds was analyzed for cell viability and phenotype. The hydrogels' materials were evaluated in an established New Zealand White (NZW) rabbit model of DDD.. The addition of ELP to TM-HA-based hydrogels resulted in a stiffer construct, which is less stiff than native NP but has time-dependant loading characteristics that may be desirable when injected into the IVD. In vitro experiments demonstrated 70% cell viability at 3 weeks with apparent maintenance of phenotype on the basis of morphologic and immunohistochemical data. The addition of ELP had a positive desirable biomechanical effect but did not have a significant positive or negative biologic effect on cell activity. The in vivo feasibility study demonstrated favorable material characteristics and biocompatibility for application as a minimally invasive injectable NP supplement.. TM-HA-based hydrogels provide a hospitable environment for human IVD cells and have material characteristics, particularly when supplemented with ELPs that are attractive for potential application as an injectable NP supplement.

Topics: Animals; Biocompatible Materials; Biomechanical Phenomena; Cell Survival; Cells, Cultured; Cross-Linking Reagents; Disease Models, Animal; Elasticity; Elastin; Feasibility Studies; Humans; Hyaluronic Acid; Hydrogels; Intervertebral Disc; Intervertebral Disc Degeneration; Magnetic Resonance Imaging; Materials Testing; Peptides; Phenotype; Polyethylene Glycols; Rabbits; Sulfhydryl Compounds; Time Factors; Tissue Engineering; Tissue Scaffolds

Enzymatic treatments were applied to rat motion segments to establish structure-function relationships and determine mechanical parameters most sensitive to simulated remodeling and degeneration. Rat caudal and lumbar disc biomechanical behaviors were evaluated to improve knowledge of their similarities and differences due to their frequent use during in vivo models. Caudal motion segments were assigned to four groups: soaked (control), genipin treated, elastase treated, and collagenase treated. Fresh lumbar and caudal discs were also compared. The mechanical protocol involved five force-controlled loading stages: equilibration, cyclic compression-tension, quasi-static compression, frequency sweep, and creep. Crosslinking was found to have the greatest effect on IVD properties at resting stress. Elastin's role was greatest in tension and at higher force conditions, where GAG content was also a contributing factor. Collagenase treatment caused tissue compaction, which impacted mechanical properties at both high and low force conditions. Equilibration creep and cyclic compression-tension tests were the mechanical tests most sensitive to alterations in specific matrix constituents. Caudal and lumbar motion segments had many similarities but biomechanical differences suggested some distinctions in collagenous structure and water transport characteristics in addition to the geometric differences. Results provide a basis for interpreting biomechanical changes observed in animal model studies of degeneration and remodeling, and underscore the need to maintain and/or repair collagen integrity in IVD health and disease.

Topics: Animals; Biomechanical Phenomena; Collagen; Collagenases; Compressive Strength; Elastin; In Vitro Techniques; Intervertebral Disc; Intervertebral Disc Degeneration; Models, Biological; Movement; Rats; Rats, Sprague-Dawley