Effects of Osteochondrin S and select connective tissue ribonucleinate components on human osteoclasts in vitro

Author:

Cantley Melissa D1,Rainsford K D2,Haynes David R1

Affiliation:

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

2. Biomedical Research Centre, Sheffield Hallam University, Sheffield, UK

Abstract

Abstract Objectives Osteochondrin S, a natural product derived from connective tissues and yeast, is used to treat osteoarthritis. The aim of this study was to determine the effect of Osteochondrin S on human osteoclast activity in vitro. Methods Osteoclasts were derived from human peripheral blood mononuclear cells stimulated with macrophage colony-stimulating factor and receptor activator of nuclear factor kappa B (RANK) ligand. Cells were treated with 23.5–587.2 ng/ml Osteochondrin S or 0.2–5 mg/ml of RNA components (synovia, placenta, intervertebral disc or cartilage). The effects on osteoclast formation and resorptive activity were assessed. Real-time polymerase chain reaction was conducted to assess the expression of key osteoclast genes. Key findings Osteochondrin S and the individual RNA extracts resulted in a concentration-dependent inhibition of human osteoclast activity. Osteochondrin S did not affect RANK, nuclear factor of activated T cells (NFATc1), osteoclast-associated receptor or cathepsin K expression. However, there was a significant (P < 0.05) reduction in mRNA expression of calcitonin receptor. Osteochondrin S treatment also significantly increased the expression of osteoclast inhibitory factor interferon-β and, interestingly, increased the expression of tumour necrosis-α-like weak inducer of apoptosis (TWEAK). Conclusions Osteochondrin S inhibited the resorptive ability of osteoclasts. These actions are likely to occur at a late stage during osteoclast formation, downstream of NFATc1. Overall, the findings show that Osteochondrin S inhibition of osteoclast activity may be responsible for its beneficial effects on diseases such as osteoarthritis.

Funder

Dyckerhoff Pharma GmbH & Co. KG

Publisher

Oxford University Press (OUP)

Subject

Pharmaceutical Science,Pharmacology

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