Regulation of cytokine-dependent calcification of cartilage tissue by NPP1 and syndecan-4

• Applicant: Professor Dr. Thomas Pap
• Subject Area: Orthopaedics, Traumatology, Reconstructive Surgery
• Term: from 2011 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 189929146

Calcification of tissue occurs physiologically during the longitudinal growth of bones but is induced also in diseases of the skeletal system such as osteoarthritis (OA). As in physiology, pathological tissue calcification is linked to chondrocyte differentiation, and the nucleotide pyrophosphatase phosphodiesterase NPP1 has been implicated in this process. Moreover, some data indicate that inflammatory factors such as interleukin (IL)-1 promote tissue calcification through suppression of NPP1. Based on previous work of our group that has linked cartilage calcification in OA to chondrocyte hypertrophy and demonstrated the involvement of the transmembrane heparan sulfate proteoglycan syndecan-4 in IL-1 signalling, we want to investigate the regulation of cartilage calcification by NPP1 and syndecan-4. Through in vitro experiments on isolated chondrocytes and osteoblasts as well as in vivo studies in NPP1- and syndecan-4 deficient mice, we want to follow the hypothesis that inflammatory mediators such as IL-1 promote tissue calcification in OA by regulating NPP1 and that syndecan-4 is involved in this process. The project will provide important insights into the role and mechanisms of pathological calcification of cartilage in the pathogenesis of OA.

• DFG Programme: Research Grants