THU0025 Expression of interleukin-20 and its receptors in osteoblasts and osteoclasts in bone tissue from patients with rheumatoid arthritis
Authors: J. Rømer, P.A. Usher, M.N. Nielsen, J. Mandelbaum, M. Jackerott
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Elevated expression of interleukin-20 (IL-20) and its receptors has been demonstrated in synovium from patients with rheumatoid arthritis (RA), and IL-20 is thought to be implicated in the pathogenesis of RA. Selective inhibition of IL-20 reduced disease activity and bone loss in rats with collagen-induced arthritis (1). In support of a role of IL-20 in bone erosion in RA, it has been demonstrated in murine cells that IL-20 stimulates expression of RANK-L in osteoblasts and RANK in osteoclasts, which leads to osteoclastogenesis and induces osteoclast activity (2) <h3>Objectives</h3> To analyse the expression and localisation of IL-20 and its receptor chains IL-20R1, IL-20R2 and IL-22R in bone samples from patients with RA using immunohistochemistry and cell identification with selected bone cell markers <h3>Methods</h3> RA bone and synovial samples were collected following joint replacement knee surgery. The bone samples were decalcified in ImmunoCal and paraffin embedded. Immunohistochemistry was performed with antibodies against IL-20 (rabbit polyclonal 2313b, Novo Nordisk), IL-20R1 (mouse monoclonal MAB11761, R&amp;D), IL-20R2 (goat polyclonal AF1788, R&amp;D) or IL-22R (goat polyclonal BAF2770, R&amp;D) and immunoreactivity was visualised with DAB. Osteoblasts were identified with an antibody against RANK-L. Osteoclasts were identified using a histochemical staining for Tartrate-Resistant Alkaline Phosphatase (TRAP). The specificity of IL-20, IL-20R1, IL-20R2 and IL-22R antibodies was validated in sections of paraffin-embedded cells transfected with IL-20, or either of the two receptor complexes IL-20R1/IL-20R2 or IL-22R/IL-20R2 <h3>Results</h3> Immunohistochemical staining of paired synovial and bone tissue samples from the same patient revealed that IL-20 is present in synovial inflammatory cells located in both the lining layer and the sublining layer as previously reported (3). In the RA bone samples, a distinct localisation of IL-20 is noted in the osteoblasts lining both trabecular and cortical bone, whereas a weaker staining of IL-20 is detected in the adjacently located osteoclasts. Immunostaining with an antibody against RANK-L showed that IL-20 and RANK-L are expressed in osteoblasts in similar patterns. Expression of all three IL-20 receptor chains were analysed in bone samples from patients with RA. In serial sections stained with anti-IL-20, anti-IL-20R1 or TRAP, it was demonstrated that IL-20R1 is expressed in trabecular TRAP-positive osteoclasts, but not in the adjacent IL-20-positive osteoblasts <h3>Conclusions</h3> IL-20 is highly expressed in osteoblasts, and IL-20R1 is found in osteoclasts in bone samples from patients with RA. In addition to the role of IL-20 in synovial inflammation, the present data supports the hypothesis that IL-20 may also be involved in bone modulation in human disease, and that neutralisation of IL-20 may lead to inhibition of bone erosion in patients with RA. A human anti-IL-20 monoclonal antibody, NNC0109-0012, is currently being studied in patients with rheumatoid arthritis <h3>References</h3> Hsu et al, Arthritis Rheum. 62:3311-21, 2010; 2 Hsu et al, J Exp Med. 208:1849-61, 2011; 3 Rømer et al, Abstract #FRI0079 at EULAR, 2009 <h3>Disclosure of Interest</h3> J. Rømer Shareholder of: Novo Nordisk, Employee of: Novo Nordisk, P. Usher Shareholder of: Novo Nordisk, Employee of: Novo Nordisk, M. Nielsen Shareholder of: Novo Nordisk, Employee of: Novo Nordisk, J. Mandelbaum Shareholder of: Novo Nordisk, Employee of: Novo Nordisk, M. Jackerott Shareholder of: Novo Nordisk, Employee of: Novo Nordisk