IKK/NF-κB and ROS signal axes are involved in Tenacissoside H mediated inhibitory effects on LPS-induced inflammatory osteolysis

Abstract

Periodontal disease and arthroplasty prosthesis loosening and destabilization are both associated with osteolysis, which is predominantly caused by abnormal bone resorption triggered by pro-inflammatory cytokines. Osteoclasts (OCs) are critical players in the process. Concerns regarding the long-term efficacy and side effects of current frontline therapies, however, remain. Alternative therapies are still required. The aim of this work was to investigate the involvement of Tenacissoside H (TDH) in RANKL-mediated OC differentiation, as well as inflammatory osteolysis and associated processes. In vitro, bone marrow-derived macrophages (BMMs) cultured with RANKL and M-CSF were used to detect TDH in the differentiation and function of OCs. Real-time quantitative PCR was used to measure the expression of specific genes and inflammatory factors in OCs. Western blot was used to identify NFATc1, IKK, NF-κB, MAPK pathway, and oxidative stress-related components. Finally, an LPS-mediated calvarial osteolysis mouse model was employed to explore TDH's role in inflammatory osteolysis. The results showed that in vivo TDH inhibited the differentiation and resorption functions of OCs and down-regulated the transcription of osteoclast-specific genes, as well as Il-1β, Il-6 and Tnf-α. In addition, TDH inhibited the IKK and NF-κB signalling pathways and down-regulated the level of ROS. In vivo studies revealed that TDH improves the bone loss caused by LPS. TDH may be a new candidate or treatment for osteoclast-associated inflammatory osteolytic disease.

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