Age-related changes in micrornas expression in mouse cruciate ligaments

Abstract

This study aims to investigate the course of cartilage aging in healthy humans over 6 years via repeated T2 MRI relaxation time measurements of the knee, which serve as surrogate markers of knee cartilage composition. Methods: Ninety-two healthy subjects with no major risk factors and no previous clinical or radiographic diagnosis of osteoarthritis (OA) were selected from the Osteoarthritis Initiative (OAI) and stratified into three age groups: 45-49 (n¼29), 50-54 (n¼28) and 55þ (n¼35) years old. All subjects were serially examined at 2-year intervals with radiography and 3T MR imaging of the right knee over a 6-year follow-up period. Sagittal two-dimensional multispin multiecho images were acquired. A semi-automated spline-based segmentation was utilized to generate compartment-specific T2 relaxation time measurements of five knee cartilage compartments: patella, lateral femur, medial femur, lateral tibia and medial tibia. Statistical analyses employed the paired Ttest, chi-square test, McNemar's test and mixed random effects models adjusted for age, sex and BMI. Results: All three age groups showed similar patterns of cartilage aging in all cartilage knee compartments. From baseline to the 2-year followup, all age groups exhibited a significant increase (p<0.05) in mean T2 values showed in most compartments. This significant increase was most pronounced in the youngest age group (age 45-49 y, p<0.05) in all five compartments. Mean T2 values at subsequent time points (year 2 through 6), remained mostly unchanged (p>0.05) compared to the 2yfollow up time point as exemplified in Fig. 1. This suggests a plateauing of mean T2 values with aging. Mixed random effects modeling demonstrated an overall nonlinear pattern of mean T2 change over time. Conclusions: This longitudinal study characterizes, for the first time, the normal long-term evolution of human knee cartilage aging by using in vivo T2 MRI relaxation time measurements as a surrogate marker for cartilage composition. The results of our study suggest that with aging, human cartilage undergoes non-linear changes in cartilage composition which seem to follow a saturation curve-like and potentially plateauing pattern. Our findings of regular cartilage aging have to be taken into account when interpreting T2 relaxation time findings in osteoarthritic studies, but need further validation in larger datasets.

Small RNA signatures of the anterior cruciate ligament from patients with knee joint osteoarthritis

“…Total RNA was extracted as above. Small non-coding RNAs were chosen based on our current work, level of differential expression (p < 0.05 and logFC> 1.2), and following a literature review of differentially expressed genes (Li et al, 2017a;Kharaz et al, 2018). PolyA cDNA was synthesized using 200 ng RNA and the miScript II RT Kit.…”