P124/O27 Osteocyte-derived podoplanin is an important regulator of bone remodelling in the KBxN serum transfer model of rheumatoid arthritis

Career situation of first and presenting author Post-doctoral fellow. Introduction Osteocytes derive from bone-forming osteoblasts and are located deep inside the bone matrix. They are encysted in cavities (lacunae) and form dendritic extensions to develop a dense sentinel network inside the bone. Osteocytes are not passive cells. They modulate bone remodelling through regulation of both osteoclast and osteoblast activity. Immature osteocytes express the transmembrane glycoprotein podoplanin (PDPN/gp38) 1 which is important for dendrite elongation and osteocyte function. 2 Moreover it has been reported that PDPN expression is regulated by inflammatory cytokines including TNFα, IL-6, IL-22, TGF-β1, IFN-γ 3 and is highly expressed in synovial tissues from RA patients. 4 However the role of PDPN in osteocytes during inflammatory disease has not previously been investigated. Objectives In this study we investigated the effect of osteocyte-specific deletion of PDPN in the KBxN serum transfer (ST) mouse model of rheumatoid arthritis. Methods Dmp1 Cre mice were crossed with PDPN flox/flox mice to generate osteocyte specific conditional knockout mice as well as appropriate PDPN flox/fox controls. KBxN ST arthritis was used to study the effect of PDPN deletion on mouse arthritis progression. PDPN expression was assessed by immunohistochemistry. Osteoclast numbers were calculated by TRAP staining. Loss of cartilage and pannus formation was evaluated by Safranin-O and H and E staining. Standard microCT and synchrotron microCT analysis was used to assess bone density parameters, osteocyte location and bone erosions. Results PDPN is expressed in osteocytes at sites of bone erosions in inflamed joints of KBxN ST mouse model. Osteocyte-specific PDPN deletion has no effect on trabecular and cortical bone density parameters in mouse tibiae under resting conditions, as has been previously reported. 2 However, loss of PDPN on osteocytes leads to significantly more bone erosions in the resolving phase of the KBxN ST model compared to non-deleted controls. Deletion of osteocyte PDPN has no effect on pannus formation, cartilage loss and osteoclast numbers. Conclusions Osteocyte-derived PDPN has been suggested as an important sensor for bone damage and this study demonstrates its bone-protective function during inflammatory arthritis. References Zhang KQ, et al. Molecular and Cellular Biology 2006;26:4539–4552. Staines KA, et al. J Cell Physiol 2017;232:3006–3019. Honma M, Minami-Hori M, Takahashi H, Iizuka HP. J Dermatol Sci 2012;65:134–140. Del Rey MJ, et al. Plos One 2014;9:e99607. Disclosure of Interest None declared.