Ains-The age-related changes in the biochemical composition of the collagenous matrix of the human lamina cribrosa were investigated. Methods-An age range (3 weeks to 92 years old) of human laminae cribrosae, dissected free of any surrounding structures which contained collagen, were analysed for collagen solubility (n= 58) total collagen content (n=46), proportion of collagen types (n=38), and collagen cross linking (n=30), using hydroxyproline analysis, scanning densitometry of peptides after cyanogen bromide digestion, and high performance liquid chromatography, respectively. Results-Age-related changes included an increase in total collagen and a decrease in the proportion of type III collagen within the lamina cribrosa. The collagen cross link pyridinoline was present at low levels, but demonstrated no trend with age. An age-related increase was found in pentosidine, an advanced glycation product. Conclusion-These changes in collagen composition imply that the mechanical properties of the lamina cribrosa are altered, resulting in a stiffer, less resilient structure with age. Such alterations in structure may contribute to the increased susceptibility of the elderly to axonal damage in chronic open angle glaucoma. (Br_7 Ophthalmol 1995; 79: 368-375)

Impingement by the ICN on the ACLs of the high risk breeds may result in increased collagen remodelling and increased sulphated GAG deposition, causing reduced structural integrity of the ligament. Altered ACL composition may predispose the ligament to increased laxity leading to joint degeneration and OA. This may have a comparative implication for pathogenesis of ACL rupture in humans.

SummaryObjectiveTo examine effects of high omega-3 (n-3) polyunsaturated fatty acid (PUFA) diets on development of osteoarthritis (OA) in a spontaneous guinea pig model, and to further characterise pathogenesis in this model. Modern diets low in n-3 PUFAs have been linked with increases in inflammatory disorders, possibly including OA. However, n-3 is also thought to increases bone density, which is a possible contributing factor in OA. Therefore we aim to determine the net influence of n-3 in disease development.MethodOA-prone Dunkin-Hartley (DH) Guinea pigs were compared with OA-resistant Bristol Strain-2s (BS2) each fed a standard or an n-3 diet from 10 to 30 weeks (10/group). We examined cartilage and subchondral bone pathology by histology, and biochemistry, including collagen cross-links, matrix metalloproteinases (MMPs), alkaline phosphatase, glycosaminoglycan (GAG), and denatured type II collagen.ResultsDietary n-3 reduced disease in OA-prone animals. Most cartilage parameters were modified by n-3 diet towards those seen in the non-pathological BS2 strain – significantly active MMP-2, lysyl-pyridinoline and total collagen cross-links – the only exception being pro MMP-9 which was lower in the BS2, yet increased with n-3. GAG content was higher and denatured type II lower in the n-3 group. Subchondral bone parameters in the DH n-3 group also changed towards those seen in the non-pathological strain, significantly calcium:phosphate ratios and epiphyseal bone density.ConclusionDietary n-3 PUFA reduced OA in the prone strain, and most disease markers were modified towards those of the non-OA strain, though not all significantly so. Omega-3 did not increase markers of pathology in either strain.

Presently, there is a lack of fundamental understanding regarding changes in collagen's molecular state due to mechanical damage. The bovine tail tendon (BTT; steers approximately 30 months) was characterized and used as an in vitro model for investigating the effect of tensile mechanical overload on collagen susceptibility to proteolysis by acetyltrypsin and alpha-chymotrypsin. Two strain rates with a 1000-fold difference (0.01 and 10 s(-1)) were used, since molecular mechanisms that determine mechanical behavior were presumed to be strain rate dependent. First, it was determined that the BTTs were normal but immature tendons. Water content and collagen content (approx. 60% of wet weight and 80% of dry weight, respectively) and mechanical properties were all within the expected range. The collagen crosslinking was dominated by the intermediate crosslink hydroxylysinonorleucine. Second, tensile overload damage significantly enhanced proteolysis by acetyltrypsin and, to a lesser degree, by alpha-chymotrypsin. Interestingly, proteolysis by acetyltrypsin was greatest for specimens ruptured at 0.01 s(-1) and seemed to occur throughout the specimen. Understanding damage is important for insight into injuries (as in sports and trauma) and for better understanding of collagen fiber stability, durability, and damage mechanisms, aiding in the development of durable tissue-based products for mechanically demanding surgical applications.