Parathyroid hormone-related protein is abundant in osteoarthritic cartilage, and the parathyroid hormone-related protein 1-173 isoform is selectivelyinduced by transforming growth factor beta in articular chondrocytes and suppresses generation of extracellular inorganic pyrophosphate

Objective. Parathyroid hormone-related protein (PTHrP) is a major, locally expressed regulator of growth cartilage chondrocyte proliferation, differen tiation, synthetic function, and mineralization, Because mechanisms that li mit cartilage chondrocytes from maturing and mineralizing are diminished in osteoarthritis (OA), we studied PTHrP expression by articular chondrocytes , Methods. PTHrP was studied in normal knee cartilage samples and cultured ar ticular chondrocytes, and in cartilage specimens from knees with advanced O A, obtained at the time of joint replacement. Results, PTHrP was more abundant in OA than in normal human knee articular cartilage. Both demonstrated PTH/PTHrP receptor expression. PTHrP 1-173, on e of three alternatively spliced PTHrP isoforms, was exclusively expressed and induced by transforming growth factor beta in cultured chondrocytes, Ch ondrocytes mainly used the GC-rich P2 alternative promoter to express PTHrP messenger RNA. Inhibition by PTHrP 1-173, but not by PTHrP 1-146 or PTHrP 1-87, of inorganic pyrophosphate (PPI) elaboration suggested selective func tional properties of the 1-173 isoform, Exposure to a neutralizing antibody to PTHrP increased PPi elaboration by articular chondrocytes. Conclusion. Increased expression of PTHrP, including the 1-173 isoform, has the potential to contribute to the pathologic differentiated functions of chondrocytes, including mineralization, in OA.