Transforming growth factor beta-1 stimulates articular chondrocyte elaboration of matrix vesicles capable of greater calcium pyrophosphate precipitation

AbstractObjective To determine the role of transforming growth factor β1 (TGFβ) in early calcium pyrophosphate formation by measuring its effects on articular chondrocyte matrix vesicle (MV) formation, specific activity of the inorganic pyrophosphate(PPi)-generating enzyme nucleoside triphosphate pyrophospho-hydrolase (NTPPPH) and biomineralization capacity.Methods MV elaborated from mature porcine chondrocyte monolayers±TGFβ were compared for protein content, NTPPPH activity, and ATP-dependent biomineralization. Precipitation of calcium pyrophosphate mineral phases by MV was determined by a radiometric assay and by Fourier transform infrared spectroscopy (FTIR).Results MV from monolayers exposed to TGFβ were enriched in NTPPPH activity compared to MV from control monolayers (P< 0.01) and precipitated more calcium/mg MV protein than controls (P≤ 0.01). FTIR spectra of mineral generated by monolayer-elaborated MV were consistent with poorly crystalline CPPD.Conclusions TGFβ is capable of increasing the capacity of articular chondrocyte-derived MV to generate PPi via NTPPPH and precipitate calcium in the form of CPPD mineral. These data support the concept that this growth factor plays a key role in cartilage matrix CPPD deposition