Age- and Gender-Dependent Changes in Connective Tissue Remodeling: Physiological Differences in Circulating MMP-3, MMP-10, TIMP-1 and TIMP-2 Level

Abstract

Background: The mechanisms which cause age-dependent remodeling of connective tissue are still not fully understood. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) constitute an important proteolytic pathway affecting physiological matrix remodeling. Objective: The way in which changes in the extracellular matrix metabolism during the ageing process influence the level of circulating MMP-3 and MMP-10, as well as their tissue inhibitors TIMP-1 and TIMP-2, in a healthy population was investigated in this study. Methods: Blood samples were taken from 81 healthy individuals aged 6–62 years and measured for MMP-3, MMP-10, TIMP-1 and TIMP-2 levels using enzyme-linked immunosorbent assays. Polyacrylamide gel electrophoresis followed by Western immunoblotting allowed for the detection of pro- and active forms of both MMPs. Results: Serum MMP-3 and TIMP-1 values were positively correlated with age (r = 0.44, p = 0.00001 and r = 0.28, p = 0.012, respectively). A contrary tendency was found for MMP-10 and TIMP-2 serum levels. A strong age-related decrease in MMP-10 (–0.53; p = 0.000) and TIMP-2 (–0.52; p = 0.000) was noticed in our study. Gender was a significant factor modifying MMP/TIMP potential, except for the MMP-10 level. Conclusions: The data presented indicate that changes in MMP/TIMP balance occur in physiological ageing. Moreover, these findings highlight the necessity of utilizing age- and sex-matched values for analysis of MMPs and TIMPs in the pathological conditions.

Role of matrix metalloproteinase-10 in the BMP-2 inducing osteoblastic differentiation

“…Because serum levels of MMP-10 in human seemed to be less than 0.5 ng/mL, as previously reported [20].…”

Possible involvement of matrix metalloproteinase-3 in the pathogenesis of macroprolactinaemia in some patients with rheumatoid arthritis

“…If MMP-3 is an independent cause of macroprolactinaemia, the effect of elevated MMP-3 levels should be added to that of ageing, resulting in a higher prevalence of macroprolactinaemia in RA patients than in the age-matched control subjects. Serum MMP-3 levels in the elderly control subjects were found to be higher than those in the young control subjects, in accordance with the previous report that serum MMP-3 values were positively correlated with age (16). Some unknown factor operating upstream of MMP-3 and ageing may be involved in the pathogenesis of macroprolactinaemia.…”

Serum Level of MMP-3 in Patients with Oral Squamous Cell Carcinoma - Lack of Association with Clinico-pathological Features

“…In this study serum MMP-3 concentration was higher in females compared to males. Komosinska-vassevk et al found different MMP-3 serum level in males and females (Komosinska-Vassev et al, 2011). These findings show the necessity of matching age and sex for analysis of MMP-3 in the pathological conditions.…”