Latent TGF-β content of articular cartilage with development and age

An important regulatory feature of transforming growth factor-β (TGF-β) in cartilage stems from its extracellular matrix (ECM) sequestration as an inactive latent complex (LTGF-β), a configuration that enables need-based activation in response to physiologic stimuli. Recent work has elucidated the dysregulation of TGF-β signaling with development, age, and pathology. However, characterizations of LTGF-β content levels in cartilage are limited. Here, we characterize the variation of LTGF-β in articular cartilage with tissue development and age.

LTGF-β evolution with development is characterized via measures of bovine cartilage explants from fetal, skeletally immature (2-4 months), and skeletally mature (60 months) animals. LTGF-β evolution with cartilage aging is characterized via measures of human cartilage explants procured via cadavers (n=19 donors) ranging in age from 13 to 80 years.

For bovine cartilage, while LTGF-β per unit tissue volume decreases with development (50.5 ± 22.0 to 16.4 ± 7.4 ng/mL for LTGF-β1; p<0.01; 29.8 ± 10.7 to 12.6 ± 4.1 ng/mL for LTGF- β2; p<0.01), LTGF-β1 and LTGF-β2 contents per cell number in the tissue does not change with development (p>0.41), indicating that the amount of LTGF-β available for each chondrocyte remains conserved. LTGF-β1 content in human tissues exhibits a dynamic range of an order of magnitude (6.4 ± 3.6 to 70.6 ± 21.8 ng/mL), but donor age is not predictive of LTGF-β1 content in cartilage (p=0.87).

These results suggest that development and aging are not limiting factors for LTGF-β availability in cartilage.