Age-Related Changes in the Musculoskeletal System and the Development of Osteoarthritis

Osteochondral (OC) repair is an extremely challenging topic due to the complex biphasic structure and poor intrinsic regenerative capability of natural osteochondral tissue. In contrast to the current surgical approaches which yield only short-term relief of symptoms, tissue engineering strategy has been shown more promising outcomes in treating OC defects since its emergence in the 1990s. In particular, the use of multizonal scaffolds (MZSs) that mimic the gradient transitions, from cartilage surface to the subchondral bone with either continuous or discontinuous compositions, structures, and properties of natural OC tissue, has been gaining momentum in recent years. Scrutinizing the latest developments in the field, this review offers a comprehensive summary of recent advances, current hurdles, and future perspectives of OC repair, particularly the use of MZSs including bilayered, trilayered, multilayered, and gradient scaffolds, by bringing together onerous demands of architecture designs, material selections, manufacturing techniques as well as the choices of growth factors and cells, each of which possesses its unique challenges and opportunities.

Growth hormone (GH) is a key mediator of skeletal growth. In humans, excess GH secretion due to pituitary adenoma, seen in patients with acromegaly, results in severe arthropathies. This study investigated the effects of long-term excess GH on the knee joint tissues. One year–old wild-type (WT) and bovine GH (bGH) transgenic mice were used as a model for excess GH. bGH mice showed increased sensitivity to mechanical and thermal stimuli, compared with WT mice. Micro–computed tomography analyses of the distal femur subchondral bone revealed significant reductions in trabecular thickness and significantly reduced bone mineral density of the tibial subchondral bone–plate associated with increased osteoclast activity in both male and female bGH compared with WT mice. bGH mice showed severe loss of matrix from the articular cartilage, osteophytosis, synovitis, and ectopic chondrogenesis. Articular cartilage loss in the bGH mice was associated with elevated markers of inflammation and chondrocyte hypertrophy. Finally, hyperplasia of synovial cells was associated with increased expression of Ki-67 and diminished p53 levels in the synovium of bGH mice. Unlike the low-grade inflammation seen in primary osteoarthritis, arthropathy caused by excess GH affects all joint tissues and triggers severe inflammatory response. Data from this study suggest that treatment of acromegalic arthropathy should involve inhibition of ectopic chondrogenesis and chondrocyte hypertrophy.

There is a clear link between increasing age and meniscus degeneration, leading to increased injury, osteoarthritis (OA) progression, and often total knee replacement. Advanced glycation end-products (AGEs) are non-enzymatic crosslinks and adducts that accumulate in collagen with age, altering tissue mechanics and cell function, ultimately leading to increased injury and inflammation. AGEs, both fluorescent and non-fluorescent, play a central role in age-related degradation of tissues throughout the body; however, little is known about their role in meniscus degeneration. The objective of this study was to characterize changes in aged OA menisci, specifically evaluating zonal AGE accumulation, to gain a better understanding of changes that may lead to age-related meniscal degeneration.

Deidentified human menisci (N = 48, 52–84 years old) were obtained from subjects undergoing total knee replacement. Changes in extracellular matrix (ECM) were assessed by gross morphology, confocal analysis, and biochemical assays. Deoxyribonucleic acid (DNA), glycosaminoglycan (GAG), collagen, and AGE accumulation were compared with patient age, zonal region, and patient sex.

There were minimal changes in DNA, GAG, and collagen concentration with age or zone. However, collagen fraying and AGEs increased with age, with more AGEs accumulating in the meniscal horns compared to the central body and in male menisci compared to females.

Overall, this work provides greater insights into regional changes that occur in human menisci with age and OA. These results suggest AGEs may play a role in the degeneration of the meniscus, with AGEs being a possible target to reduce age-related tears, degeneration, and OA progression.