Function and Regulation of the Transmembrane Glycoprotein Podoplanin in Inflammatory Bone Destruction in Rheumatoid Arthritis
Final Report Abstract
In this research project the function and regulation of the transmembrane glycoprotein podoplanin (PDPN) during the pathogenesis of rheumatoid arthritis (RA) should be investigated. RA is an autoimmune disease characterized by inflammation, pain, and swelling of the joints. Moreover, there is a progressive destruction of the articular cartilage and bone in the course of this disease. Osteocytes are descendants of matrix-producing osteoblasts embedded inside the bone and play a key role in regulation of both osteoclast and osteoblast activity. During their embedding phase, osteocytes are encysted in cavities (lacunae) and build dendritic extensions which are located in tunnels called canaliculi to build a dense network inside the bone. It is assumed that osteocyte morphology is controlled by PDPN1. Recently it has been shown that deletion of PDPN in osteocytes leads to shorter dendrites, which could have a huge impact on the osteocyte network formation and their communication with the surrounding environment influencing bone remodelling. The aim of this project was to investigate the role of PDPN in osteocytes on bone homeostasis and how it affects bone destruction during RA. For this purpose, mice possessing an osteocyte-specific deletion of PDPN were injected with serum from K/BxN mice to develop an acute RA. The results from this project strongly suggest that PDPN positive osteocytes are up regulated in regions of bone damage in mouse models of inflammatory arthritis. Moreover loss of PDPN leads to enhanced bone erosion in the resolving phase of the K/BxN serum transfer model of RA. In summary, PDPN expression by osteocytes is important for bone integrity perhaps through osteocyte activation during inflammatory arthritis. The role of PDPN in osteocytes requires further investigation; it might be essential for osteoblast-to-osteocyte differentiation, for the organisation of the osteocyte network and for the regulation of bone homeostasis under inflammatory conditions.
Publications
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The role of stromal cells in inflammatory bone loss. Clinical and Experimental Immunology (2017)
Wehmeyer C, PapT, Buckley CD, Naylor AJ
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Endogenous Galectin-9 Suppresses Apoptosis in Human Rheumatoid Arthritis Synovial Fibroblasts. Scientific Reports (2018)
Pearson M, Bik M, Ospelt C, Naylor A, Wehmeyer C, Jones S, Buckley CD, Gay S, Filer A, Lord J
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European Workshop for Rheumatology Research, Lyon, France. P124/O27 Osteocyte-derived podoplanin is an important regulator of bone remodelling in the K/BxN serum transfer model of rheumatoid arthritis (2019)
Wehmeyer C, Naylor AJ, Möller K, Poologasundarampillai G, Pap T, Buckley CD
