![]() ![]() The resident cells of different musculoskeletal tissues making up a given articular joint ( i.e. An understanding of changes to molecular transport associated with aging and disease of musculoskeletal organs, such as the knee joint, may have important implications for unraveling the etiology and pathogenesis of osteoarthritis (OA) and other degenerative diseases associated with aging. Molecular transport between tissue compartments of the musculoskeletal system occurs via blood, interstitial fluid and lymphatic flow 5, 6. The role of size selectivity in the onset and progression of OA is unknown. Osteoarthritis (OA), a degenerative disease of the musculoskeletal system and the most common cause of disability in aging adults, is a multifactorial disease involving complex interactions between tissues of articular joints and the immune system. A recent study correlates aging with increased intestinal permeability to solutes but not macromolecules, which modulates “innate mucosal immune responsiveness elderly humans“ 3. Tissues of the brain 1, lung 2 and gut 3 exhibit the functional barrier property of molecular size selectivity, which is essential for normal physiologic function throughout life 4. This study opens up new avenues for study of musculoskeletal physiology in health and disease as well as new strategies for drug delivery. Small caliber channels through the articular cartilage appeared to show a degree of green fluorescence not observed in the surrounding cartilage matrix. Surprisingly, muscle fiber bundles exhibited little fluorescence, while their bounding fasciae fluoresced either red or green. Tissues of the meniscus, ligament, and tendon exhibited abundant 10 kDa tracer volumes of tissue containing this molecular tracer were significantly lower in older than in younger animals. The larger, 70 kDa red tracer was abundant in the marrow cavity albeit less prevalent or absent in the bone, cartilage, meniscus and other tissues of the joint. A remarkable separation of the molecules was observed in serial fluorescent images of whole joint sections. We quantified tracer transport in serial-sectioned, cryofixed block specimens after five minutes’ circulation. Here we delivered a mixture of Texas-red (70 kDa), and Rhodamine-green (10 kDa) tagged, dextrans of neutral charge in a single bolus via heart injection to middle aged (8–10 months) and aged (17–19 months) Dunkin-Hartley Guinea pigs, a natural model for OA. The role of molecular size selectivity in the onset and progression of osteoarthritis (OA), a degenerative disease of the musculoskeletal system and the most common cause of disability in aging adults, is unknown. ![]()
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