Inhibitory effects of sodium pentosan polysulfate on formation and function of osteoclasts derived from canine bone marrow.

Autor: Wijekoon HMS; Department of Veterinary Clinical Sciences, Laboratory of Veterinary Surgery, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, 060-0818, Japan. suranjisk@gmail.com., Bwalya EC; Department of Veterinary Clinical Sciences, Laboratory of Veterinary Surgery, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, 060-0818, Japan., Fang J; Department of Veterinary Clinical Sciences, Laboratory of Veterinary Surgery, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, 060-0818, Japan., Kim S; Department of Veterinary Clinical Sciences, Laboratory of Veterinary Surgery, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, 060-0818, Japan., Hosoya K; Department of Veterinary Clinical Sciences, Laboratory of Veterinary Surgery, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, 060-0818, Japan., Okumura M; Department of Veterinary Clinical Sciences, Laboratory of Veterinary Surgery, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, 060-0818, Japan.
Jazyk: angličtina
Zdroj: BMC veterinary research [BMC Vet Res] 2018 May 02; Vol. 14 (1), pp. 152. Date of Electronic Publication: 2018 May 02.
DOI: 10.1186/s12917-018-1466-4
Abstrakt: Background: Sodium pentosan polysulfate (NaPPS) was testified as a chondroprotective drug in with a detailed rationale of the disease-modifying activity. This study was undertaken to determine whether anti-osteoarthritis drug, NaPPS inhibited osteoclasts (OC) differentiation and function. Canine bone marrow mononuclear cells (n = 6) were differentiated to OC by maintaining with receptor activator of nuclear factor kappa B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) for up to 7 days with the treatment of NaPPS at concentration of 0, 0.2, 1 and 5 μg/mL. Differentiation and function of OC were accessed using tartrate-resistant acid phosphate (TRAP) staining and bone resorption assay, while monitoring actin ring formation. Invasion and colocalization patterns of fluorescence-labeled NaPPS with transcribed gene in OC were monitored. Gene expression of OC for cathepsin K (CTK), matrix metallopeptidase-9 (MMP-9), nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), c-Fos, activator protein-1(AP-1) and carbonic anhydrase II was examined using real-time PCR.
Results: Significant inhibition of OC differentiation was evident at NaPPS concentration of 1 and 5 μg/mL (p < 0.05). In the presence of 0.2 to 5 μg/mL NaPPS, bone resorption was attenuated (p < 0.05), while 1 and 5 μg/mL NaPPS achieved significant reduction of actin ring formation. Intriguingly, fluorescence-labeled NaPPS invaded in to cytoplasm and nucleus while colocalizing with actively transcribed gene. Gene expression of CTK, MMP-9 and NFATc1 were significantly inhibited at 1 and 5 μg/mL (p < 0.05) of NaPPS whereas inhibition of c-Fos and AP-1 was identified only at concentration of 5 μg/mL (p < 0.05).
Conclusions: Taken together, all the results suggest that NaPPS is a novel inhibitor of RANKL and M-CSF-induced CTK, MMP-9, NFATc1, c-Fos, AP-1 upregulation, OC differentiation and bone resorption which might be a beneficial for treatment of inflammatory joint diseases and other bone diseases associated with excessive bone resorption.
Databáze: MEDLINE
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