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.
Highlights
In 1744, William Hunter wrote of articular cartilage, that “when destroyed, it is never recovered” [1]
Analysis of 8 sections taken from the same location in each joint show that adult cartilage is 30% thinner: average thickness 425 μm for juvenile cartilage and 303 μm for adult cartilage
The osteochondral junction is smoother in the adult cartilage compared with juvenile cartilage
Summary
In 1744, William Hunter wrote of articular cartilage, that “when destroyed, it is never recovered” [1]. Cartilage regeneration has been reported following articular cartilage injury in 3-month-old rabbits, but not in adult animals [5] This inability of adult cartilage to regenerate could be due to either or both reduced proliferative or extracellular matrix synthetic capacities of adult chondrocytes [6]. Absence of growth factors does not account for these changes, but they are partially reversible in 3-dimensional culture [10] This tendency of chondrocytes to lose their phenotype may explain the limited benefit of current cell-based therapies for cartilage injuries. The purpose of the work described in this paper was firstly to measure the differences in mRNA and protein expression of type II collagen and aggrecan, the main proteoglycan, and the regulatory transcription factors Sox , and 9 between adult and juvenile articular cartilage. We chose to use pigs for the study because their joints are of a similar size to human, and their forefeet, which are obtained from an abattoir, provide cartilage from weight-bearing joints of animals of specific ages, allowing replication of samples
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