Hydration status significantly affects the toughness of bone. In addition to the collagen phase, recent evidence shows that glycosaminoglycans (GAGs) of proteoglycans (PGs) in the extracellular matrix also play a pivotal role in regulating the tissue-level hydration status of bone, thereby affecting the tissue-level toughness of bone. In this study, we hypothesized that the amount of GAGs in bone matrix decreased with age and such changes would lead to reduction in bound water and subsequently result in a decrease in the tissue-level toughness of bone. To test the hypothesis, nanoscratch tests were conducted to measure the tissue-level toughness of human cadaveric bone specimens, which were procured only from male donors in three different age groups: young (26 ± 6 years old), mid-aged (52 ± 5 years old) and elderly (73 ± 5 years old), with six donors in each group. Biochemical and histochemical assays were performed to determine the amount and major subtypes of GAGs and proteoglycans in bone matrix. In addition, low-field NMR measurements were implemented to determine bound water content in bone matrix. The results demonstrated that aging resulted in a statistically significant reduction (17%) of GAGs in bone matrix. Concurrently, a significant deterioration (20%) of tissue-level toughness of bone with age was observed. Most importantly, the deteriorated tissue-level toughness of bone was associated significantly with the age-related reduction (40%) of bound water, which was partially induced by the decrease of GAGs in bone matrix. Furthermore, we identified that chondroitin sulfate (CS) was a major subtype of GAGs and the amount of CS decreased with aging in accompany with a decrease of biglycan that is a major subtype of PGs in bone. The findings of this study suggests that reduction of GAGs in bone matrix is likely one of the molecular origins for age-related deterioration of bone quality.

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Objective: This study was undertaken to assess whether advanced glycation end-products had any influence on the levels of matrix metalloproteinase-1 in patients with type-II diabetes mellitus and chronic periodontitis. Material & Methods: It was a case-control study. 30 subjects were recruited in test group, who had chronic periodontitis and known cases of type-II diabetes mellitus. 30 subjects were kept in control group, who had chronic periodontitis but no systemic diseases. Periodontal parameters were recorded, samples of saliva were collected for all the subjects, and assessment of matrix metalloproteinase-1 levels was undertaken via enzyme linked immunosorbent assay. Statistical analysis was done using SPSS 26. Results: The levels of matrix metalloproteinase-1 showed a significant elevation in test group in comparison to the controls (p<0.001). Likewise, all the periodontal parameters had greater readings in the test group as compared to the controls (p<0.05). Conclusions:As there is a significant increase in the levels of salivary matrix metalloproteinase-1 due to advanced glycation end-products, as released in diabetic subjects, the destruction of periodontal apparatus was also, in return, greater in the diabetic subjects as compared to non-diabetic ones. This proves that advanced glycation end-products further elevate the levels of matrix metalloproteinase-1 in humans, resulting in greater destruction of periodontium. Clinical Relevance:This study observes that if MMP-1 is inhibited by tissue inhibitors of metalloproteinases (TIMPs), the periodontal destruction in patients of type-II diabetes mellitus can be controlled and vice versa.