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Osteoclast-Associated Receptor (OSCAR) Distribution in the Synovial Tissues of Patients with Active RA and TNF-α and RANKL Regulation of Expression by Osteoclasts In Vitro

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Abstract

Osteoclast-associated receptor (OSCAR) is a co-stimulatory receptor in osteoclastogenesis. Synovial tissues from active rheumatoid arthritis (RA) patients express higher levels of OSCAR compared with osteoarthritic and normal patients; however, the comparison of OSCAR levels in different regions of active RA synovium has not been reported. The regulation of OSCAR by TNF-α and receptor activator of NF kappa β ligand (RANKL) in pre-osteoclasts/osteoclasts in vitro is unclear. OSCAR and tartrate-resistant acid phosphatase (TRAP) expression levels did not differ between the cartilage pannus junction (CPJ) and non-CPJ regions in active RA. We demonstrate a similar pattern of OSCAR expression in the CPJ and non-CPJ synovial tissue from patients with active RA. OSCAR was associated with mononuclear cells in both the lining and sub-lining and endothelial cells (von Willebrand factor positive). Pre-osteoclasts (TRAP-positive cells) were present in the lining and sub-lining of both regions. OSCAR messenger RNA (mRNA) expression and release by pre-oscteoclasts/osteoclasts was modulated by RANKL with/without TNF-α in vitro. Osteoclast resorption on dentine slices was significantly greater with TNF-α pre-treatment and RANKL (10 ng/ml) than RANKL 10 or 50 ng/ml alone or RANKL 10 ng/ml with TNF-α given from day 3 post-RANKL. The lower levels of OSCAR mRNA expression corresponded with high osteoclast activity levels.

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ACKNOWLEDGEMENTS

This project was funded by the Allan and Beryl Stephens Grant from Arthritis Australia and an American Society for Bone Mineral Research (ASBMR) Grant in Aid Project Grant. We would like to thank Mrs. Helen Weedon from Rheumatology at the Repatriation General Hospital for providing patient information and histological preparation of the samples.

Author information

Author notes

  1. AASSK Dharmapatni and K. Algate contributed equally to this study.

Authors and Affiliations

  1. Discipline of Anatomy and Pathology, Adelaide Medical School, The University of Adelaide, Adelaide, 5005, Australia

    Anak A. S. S. K. Dharmapatni, Kent Algate, Roxanne Coleman & Tania N. Crotti

  2. School of Population Health, Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, 5005, Australia

    Michelle Lorimer

  3. Discipline of Physiology, Adelaide Medical School, The University of Adelaide, Adelaide, SA, 5005, Australia

    Melissa D. Cantley

  4. Myeloma Research Laboratory, Cancer Theme, SAHMRI, Adelaide, SA, 5000, Australia

    Melissa D. Cantley

  5. Repatriation General Hospital, Daw Park, Adelaide, SA, Australia

    Malcolm D. Smith & Mihir D. Wechalekar

  6. Flinders Medical Centre and Flinders University, Bedford Park, SA, Australia

    Malcolm D. Smith & Mihir D. Wechalekar

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  1. Anak A. S. S. K. Dharmapatni
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  2. Kent Algate
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  8. Tania N. Crotti
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Contributions

K.A. and M.C. designed and K.A. performed the in vitro experiments with peripheral blood mononuclear cells including analysis of gene expression, TRAP staining and resorption. T.C., A.D. and R.C. designed and performed experiments with the clinical samples. M.W. and M.S. performed clinical analyses and interpretation. M.L. performed and directed statistical analyses. All authors contributed to the writing of the manuscript and approved the final version.

Corresponding author

Correspondence to Tania N. Crotti.

Ethics declarations

Ethics approval was obtained from the Repatriation Hospital, Daw Park, SA (100911b) and the Southern Adelaide Clinical Human Research Ethics Committee (199.10) for synovial tissue collection. Ethics for obtaining human PBMCs from the Australian Red Cross Blood Service was through the University of Adelaide Human Ethics Committee (H-35-2001), in accordance with National Health and Medical Research Council of Australia guidelines. Informed written consent was obtained from all patients.

Conflict of Interest The authors declare that they have no conflict of interest.

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Dharmapatni, A.A.S.S.K., Algate, K., Coleman, R. et al. Osteoclast-Associated Receptor (OSCAR) Distribution in the Synovial Tissues of Patients with Active RA and TNF-α and RANKL Regulation of Expression by Osteoclasts In Vitro . Inflammation 40, 1566–1575 (2017). https://doi.org/10.1007/s10753-017-0597-2

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