| Summary: | Biomaterials are used as implants for bone and dental disabilities. However, wear particles from the implants cause osteolysis following total joint arthroplasty (TJA). Ceramic implants are considered safe and elicit a minimal response to cause periprosthetic osteolysis. However, few reports have highlighted the adverse effect of ceramic particles such as alumina (Al<sub>2</sub>O<sub>3</sub>) on various cell types. Hence, we aimed to investigate the effect of Al<sub>2</sub>O<sub>3</sub> particles on osteoprogenitors. A comparative treatment of Al<sub>2</sub>O<sub>3</sub>, Ti, and UHMWPE particles to osteoprogenitors at a similar concentration of 200 μg/mL showed that only Al<sub>2</sub>O<sub>3</sub> particles were able to suppress the early and late differentiation markers of osteoprogenitors, including collagen synthesis, alkaline phosphatase (ALP) activity and mRNA expression of Runx2, OSX, Col1α, and OCN. Al<sub>2</sub>O<sub>3</sub> particles even induced inflammation and activated the NFkB signaling pathway in osteoprogenitors. Moreover, bone-forming signals such as the WNT/β-catenin signaling pathway were inhibited by the Al<sub>2</sub>O<sub>3</sub> particles. Al<sub>2</sub>O<sub>3</sub> particles were found to induce the mRNA expression of WNT/β-catenin signaling antagonists such as DKK2, WIF, and sFRP1 several times in osteoprogenitors. Taken together, this study highlights a mechanistic view of the effect of Al<sub>2</sub>O<sub>3</sub> particles on osteoprogenitors and suggests therapeutic targets such as NFĸB and WNT signaling pathways for ceramic particle-induced osteolysis.
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