Journal
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
Volume 17, Issue 5, Pages 1382-1394Publisher
IVYSPRING INT PUBL
DOI: 10.7150/ijbs.53992
Keywords
Sirtuin 3; peri-prosthetic osteolysis; osteoclasts; inflammatory factors
Categories
Funding
- National Natural Science Foundation of China [82072425, 82072498, 81873991, 81873990, 81672238, 81472077]
- Young Medical Talents of Jiangsu Province [QNRC2016751]
- Natural Science Foundation of Jiangsu Province [BK20180001]
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
- Program for Talents in Science and Education of Suzhou [KJXW2018079]
- clinical Key Disease Diagnosis and Treatment Technology Project of Suzhou [LCZX201824, LCZX202003]
- Science and Technology Development Plan Project of Changshu [CS201819]
- Science and Technology Plan Project of Changshu Municipal Health Committee [csws201907]
- Science and Technology Development Plan (People's livelihood Technology - Health applied basic research) of Suzhou [SYSD2018063]
- Cultivation Research Project of Suzhou Kowloon Hospital [JL201806]
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Inhibition of SIRT3 can reduce titanium particle-induced osteolysis and bone loss, potentially through decreasing osteoclast differentiation and phosphorylation levels of JNK and ERK.
Implant-derived wear particles can be phagocytosed by local macrophages, triggering an inflammatory cascade that can drive the activation and recruitment of osteoclasts, thereby inducing peri-prosthetic osteolysis. Efforts to suppress pro-inflammatory cytokine release and osteoclastsogenesis thus represent primary approaches to treating and preventing such osteolysis. Sirtuin 3 (SIRT3) is a NAD+-dependent deacetylases that control diverse metabolic processes. However, whether SIRT3 could mitigate wear debris-induced osteolysis has not been reported. Herein we explored the impact of the SIRT3 on titanium particle-induced osteolysis. Tartrate resistant acid phosphatase (TRAP) staining revealed that the inhibition of SIRT3 suppressed nuclear factor-KB ligand (RANKL)-mediated osteoclasts activation in a dose-dependent fashion. Notably, inhibition of SIRT3 also suppressed matrix metallopeptidase 9 (MMP9) and nuclear factor of activated T-cell cytoplasmic 1 (NFATc1) expression at the mRNA and protein levels, while also inhibiting the mRNA expression of dendritic cell-specific transmembrane protein (DC-STAMP), ATPase H+ Transporting V0 Subunit D2 (Atp6v0d2), TRAP and Cathepsin K (CTSK) . In addition, inhibition of SIRT3 suppressed titanium particle-induced tumor necrosis factor-alpha (TNF-?), interleukin-1? (IL-1?) and interleukin-6 (IL-6) expression and prevented titanium particle-induced osteolysis and bone loss in vivo. This inhibition of osteoclasts differentiation was found to be linked to the downregulation and reduced phosphorylation of JNK and ERK. Taken together, inhibition of SIRT3 may be a potential target for titanium particle-induced bone loss.
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