The Effects of Age and Cell Isolation on Collagen II Synthesis by Articular Chondrocytes: Evidence for Transcriptional and Posttranscriptional Regulation

Abstract

Adult articular cartilage synthesises very little type II collagen in comparison to young cartilage. The age-related difference in collagen II synthesis is poorly understood. This is the first systematic investigation of age-related differences in extracellular matrix synthesis in fresh articular cartilage and following isolation of chondrocytes. A histological comparison of 3-year-old skeletally mature and 6-month-old juvenile porcine cartilage was made. Differences in collagen II, aggrecan, and Sox5, 6, and 9 mRNA and protein expression and mRNA stability were measured. Adult cartilage was found to be thinner than juvenile cartilage but with similar chondrocyte density. Procollagen α1(II) and Sox9 mRNA levels were 10-fold and 3-fold reduced in adult cartilage. Sox9 protein was halved and collagen II protein synthesis was almost undetectable and calculated to be at least 30-fold reduced. Aggrecan expression did not differ. Isolation of chondrocytes caused a drop in procollagen α1(II) and Sox9 mRNA in both adult and juvenile cells along with a marked reduction in Sox9 mRNA stability. Interestingly, juvenile chondrocytes continued to synthesise collagen II protein with mRNA levels similar to those seen in adult articular cartilage. Age-related differences in collagen II protein synthesis are due to both transcriptional and posttranscription regulation. A better understanding of these regulatory mechanisms would be an important step in improving current cartilage regeneration techniques.