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Objectives: To investigate whether treatment with a bisphosphonate would influence the subchondral bone plate stiffness and the development of cartilage damage in Dunkin Hartley guinea pigs, which develop osteoarthritis (OA) spontaneously., Method: Fifty-six 3-month-old male Dunkin Hartley guinea pigs were randomized into a baseline group and six groups receiving either the bisphosphonate risedronate (30 µg/kg) or vehicle five times a week for 6, 12, or 24 weeks. The medial condyle of the right stifle joint was investigated by histology, using the Osteoarthritis Research Society International (OARSI) score, along with static and dynamic histomorphometry. The subchondral bone plate of the left tibia was tested mechanically with indentation testing. Degradation products of C-terminal telopeptides of type II collagen (CTX-II) were measured in serum., Results: The OARSI score did not differ between risedronate-treated and control animals at any time point. The fraction of bone surfaces covered with osteoclasts (Oc.S/BS) was significantly suppressed in risedronate-treated animals at all time points, as were the fractions of mineralizing surfaces (MS/BS) and osteoid-covered surfaces (OS/BS), and also serum CTX-II. This was accompanied by a significant increase in the epiphyseal content of calcified tissue and in the thickness of the subchondral bone plate. However, this did not result in a stiffer subchondral bone at any time point., Discussion: The risedronate treatment inhibited osteoclastic resorption of calcified cartilage in the primary spongiosa under the epiphyseal growth plate, explaining the risedronate-mediated decrease in CTX-II. Moreover, the serum CTX-II level was not related to the OA-induced articular cartilage degradation seen in this model., Conclusions: Risedronate did not influence the OARSI score and subchondral plate stiffness, but decreased serum CTX-II in Dunkin Hartley guinea pigs.

Objectives: To describe the age-related changes of articular cartilage, subchondral bone morphology, and stiffness. Furthermore, to investigate whether subchondral bone histological and mechanical properties and meniscal histological properties are related to articular cartilage damage in the Dunkin Hartley guinea pig model of osteoarthritis (OA)., Methods: Forty male Dunkin Hartley guinea pigs aged 2, 6, 9, and 12 months were studied. The right stifle joints and the left menisci were embedded undecalcified and the tibial articular cartilage and subchondral bone and the menisci were examined using histology. The stiffness of the left tibial subchondral bone was determined with indentation testing., Results: The Osteoarthritis Research Society International (OARSI) grade of the osteoarthritic cartilage lesions of the medial (p < 0.001) and lateral (p < 0.001) condyle and the ossification of the medial (p < 0.001) and lateral (p < 0.001) meniscus increased significantly with age and was significantly more pronounced at the medial condyle than at the lateral condyle. The grade of the osteoarthritic cartilage lesions was significantly correlated (r  =  0.78, p < 0.001) with the meniscal ossification, weakly correlated (r  =  0.34, p < 0.007) with the subchondral bone plate thickness, and not correlated with the subchondral bone density (r  =  -0.010, p  =  0.94) and the subchondral bone stiffness (r  =  -0.13, p  =  0.30)., Conclusion: The meniscal ossification observed in Dunkin Hartley guinea pigs may play an important role in the pathogenesis of OA in these animals.

Purpose: Several procedures in cataract surgery carry the risk of high temperature increases in the capsular bag. The present study was undertaken to determine the shrinkage temperature of the human lens capsule and to investigate the effect of temperature on the mechanical behavior of the lens capsule., Method: Thermal-shrinkage characteristics of the lens capsule were determined during gradual heating of circular specimens (2 mm in diameter) prepared from anterior lens capsules from 25 human donors, ranging in age from 20 to 98 years. Uniaxial mechanical testing was carried out at 22 degrees C, 36 degrees C and 61 degrees C on ring-shaped test specimens prepared from anterior lens capsules from 5- to 6-month-old pigs., Results: The mean shrinkage temperature (Ts) for the human lens capsule was 51.5 degrees C (range 49.3-54.3) and the mean shrinkage area in percent of the original area (AST) was 49% (36-66). Ts was significantly associated with the age of the donors and decreased 0.1 degree C per year until age 65 after which Ts was found to increase. AST showed no association with age. The mechanical effect of temperatures below the shrinkage temperature was modest. The capsule became slightly more extensible with increasing temperature. The effect of temperatures above the shrinkage temperature was an increased ultimate strain, a reduced ultimate stiffness and a slightly reduced ultimate stress., Conclusion: Thermal stability of the human lens capsule (type IV collagen) seems to be considerably lower than that of fibrous connective tissue (type I collagen). A potential risk of capsular shrinking has to be taken into account when the capsule is exposed to thermal stress during cataract surgery.

Previous findings indicate that the thermal stability of bone collagen is related to age. In this study, collagen from rat bone with reported different turnover rates was investigated. Cortical and trabecular bone from femur were obtained from intact, ovariectomized, orchidectomized and multiparous breeder rats. Thermal stabilities of fibrillar collagen in decalcified bone matrix and molecular collagen obtained by pepsin treatment were measured as shrinkage (Ts) and 'melting' temperature (Tm), respectively. Both Ts and Tm of cortical collagen from intact female rats decreased in parallel with age as previously found in male rats indicating that Ts and Tm measurements are interchangeable techniques in characterizing the thermal stability of bone collagen. Tm of trabecular collagen from intact rats decreased with age, however, with a decay only one-third of that for cortical collagen. The different rates possibly reflect different ages of collagen due to remodeling activity present in trabecular and minimal in cortical bone. Compared with control rats the Tm of trabecular collagen from gonadectomized and multiparous rats with a reported increased trabecular turnover rate was elevated, whereas only minor variations in Tm of cortical collagen were found. In conclusion, the thermal stability of bone collagen decreases with the age of the collagen. Increased bone turnover implies elevated thermal stability of bone collagen. Thus, thermal stability of bone collagen appears to be an indicator of bone turnover.

The biomechanical properties of the cervix uteri of the rat were studied under different pharmacological conditions. Four groups of rats were enrolled: A. non-pregnant (N = 12), B. 18 days pregnant treated with vehicle (N = 14), C. 18 days pregnant treated with the antigestagen ZK 98 299 (Onapristone) for 19 hours (N = 15), D. 22 days pregnant during spontaneous labor (N = 12). Load-dimension curves of two 2 mm ring-preparations from each cervix were obtained by a material testing machine. The results showed that the sampling position, the cervical ripening process, and the influence of antigestagen treatment were reflected in the biomechanical and compositional parameters. In conclusion the methodology in the present study constitute a model in which the effect of pharmaca on cervical ripening can be tested. The study demonstrated that antigestagen treatment induced biomechanical changes in the cervix comparable to those occurring during physiological cervical ripening at term.

A quantitative histologic analysis of the striated anal sphincter of 24-month-old virgin female rats was performed to evaluate the effect of oophorectomy and estrogen substitution. The oophorectomized rats had a 21% (11-31%, 95% confidence limits) reduction in the cross-sectional area of the striated muscle tissue compared with controls. This was due to a reduction in the mean cross-sectional area of the muscle fiber, whereas the number of fibers was unchanged. Although the relative amount of stromal tissue was increased in the oophorectomized rats, the total stromal tissue was unchanged. No difference in the cross-sectional area of muscle tissue was found between the estrogen-substituted, oophorectomized rats and controls. This indicates that the estrogen depletion in the oophorectomized rats has induced the reduction in muscle tissue in the striated anal sphincter.

A quantitative histologic analysis of the striated anal sphincter of virgin female rats aged 2 months and 24 months was performed to evaluate age-related changes. A 27% (8% to 46%, 95% confidence limits) increase in the cross-sectional area of the muscle in the older rats was observed compared with the young. This was due to an increase in both muscle and connective tissue. There was hypertrophy of both the small and large muscle fibres without change in the number with age. No evidence of age-related degenerative changes in this muscle in the virgin female rat was found.

Mechanical stability was examined in rat tail tendons after in vitro incubation in glucose at pH 7.4 using buffer systems of either phosphate or tris(hydroxymethyl)aminomethan. In the phosphate buffer system glucose and fluorescent compounds were found to be attached to the collagen molecules and the maximum 'stress' of the tendons was increased. In the tris(hydroxymethyl)aminomethan buffer system glucose was attached to the collagen molecules, but only small amounts of fluorescent compounds were attached to the collagen molecules and no changes in mechanical parameters were recorded. Initial incubation of tendons in a high concentration of glucose followed by incubation in either phosphate or tris(hydroxymethyl)aminomethan buffer solutions resulted in equal attachment of glucose to the collagen, but only the collagen reincubated in phosphate buffer developed a relatively high amount of fluorescent compounds and an increase in maximum mechanical 'stress' compared to the collagen reincubated in tris(hydroxymethyl)aminomethan buffer. This shows that the non-enzymatic glycosylation per se does not necessarily influence the mechanical properties of collagen. Additional reactions like transformation of glucose into fluorescent compounds or browning reaction products by Maillard's reaction seem to be essential.

Acid extracted collagen from rat skin was reconstituted into fibrils at physiological pH and ion concentration. The fibrils were indistinguishable from native collagen in ultrastructural appearance. This report describes a procedure for reconstituting collagen fibrils into thin membranes which allows the preparation of a set of collagen membranes with identical mechanical properties. Reconstituted collagen fibrils showed a gain in mechanical strength upon maturation in vitro similar to the increase in mechanical strength known to occur during maturation of collagenous tissues in vivo. It is suggested that the changes in the mechanical properties of reconstituted collagen fibrils during in vitro maturation may reflect the changes observed during in vivo maturation of collagenous tissues. The possible influence of the amounts of reducible intermolecular cross-links on the gain in strength during maturation is discussed.

The mechanical properties of membranes composed of fibrils reconstituted from solubilized and purified rat skin collagen were investigated following the addition of various concentrations of dermatan sulfate. Dermatan sulfate was added to collagen 48 hrs before and immediately after aggregation into fibrils and was added to membranes prematured for various time periods. Dermatan sulfate reduced the mechanical strength developed below the levels observed for control membranes during maturation. The stiffness was analyzed as a function of strain and for each increment of per cent strain was expressed in relation to the maximum stiffness of the membrane under consideration. When dermatan sulfate was added to the membranes in concentrations that were the same or higher than those in skin (about 1%) an increase in the relative stiffness was observed during the first part of the deformation. The length of time that the membranes were matured before the addition of dermatan sulfate did not correlate with any of the effects of dermatan sulfate.