Protective effect of zinc supplementation on tricalcium phosphate particles‐induced inflammatory osteolysis in mice. Issue 11 (25th July 2022)

• Record Type: Journal Article
• Authors: Yang, Pei; Zhang, Tao; Zhu, Ruirong; Shen, Yuchen; Pan, Yuefang; Zhang, Yun
• Is Part Of: Microscopy research and technique. Volume 85:Issue 11(2022)
• Page Start: 3608
• Page End: 3617
• Publication Date: 2022-07-25
• Subjects: ER stress -- osteoclastogenesis -- osteolysis -- TCP particles -- ZnTCP particles; Electron microscopy -- Technique -- Periodicals; Microscopy -- Periodicals; Microscopy -- Technique -- Periodicals; 502.825
• DOI: 10.1002/jemt.24213
• Languages: English
• ISSNs: 1059-910X

Abstract

Abstract: Zinc (Zn), an essential trace element, can stimulate bone formation and inhibit osteoclastic bone resorption, which controls the growth and maintenance of bone. However, the effect of Zn supplementation on tricalcium phosphate (TCP) wear particles‐induced osteolysis remains unknown. Here, we doped Zn into TCP particles (ZnTCP), and explore the protective effects of Zn on TCP particles‐induced osteolysis in vivo. TCP particles and ZnTCP particles were embedded under the periosteum around the middle suture of the mouse calvaria. After 2 weeks, blood, the periosteal tissue, and the calvaria were collected to determine serum levels of Zn and osteocalcin, pro‐inflammatory cytokines, bone biochemical markers, osteoclastogenesis and bone resorption area, and to explain its mechanism. Data revealed that Zn significantly prevented TCP particles‐induced osteoclastogenesis and bone loss, and increased bone turnover. The Zn supplement remarkably suppressed the release of pro‐inflammatory cytokines including tumor necrosis factor (TNF)‐α, interleukin (IL)‐1β, and IL‐6. Immunoblotting demonstrated that Zn alleviated expression levels of ER stress‐related proteins such as glucose‐regulated protein 78 (GRP78), PKR‐like ER kinase (PERK), phospho‐PERK (p‐PERK), eukaryotic initiation factor 2α (eIF2α), phospho‐eIF2α (p‐eIF2α), activating transcription factor 4 (ATF4), inositol‐requiring enzyme 1α (IRE1‐α) and transcription factor X‐box binding protein spliced (XBP1s), leading to decreasing the ratios of p‐PERK/PERK and p‐eIF2α/eIF2α. Taken together, Zn supplementation strongly prevents TCP particles‐induced periprosthetic osteolysis via inhibition of the ER stress pathway, and it may be a novel therapeutic approach for the treatment of aseptic prosthesis loosening. Abstract : Zn supplementation alleviated TCP particles‐induced activation of the ER stress pathway, and reduced the production of pro‐inflammatory cytokines including TNF‐α, IL‐1β and IL‐6, which prevented osteoclastogenesis and periprosthetic osteolysis caused by TCP particles. This study presents a novel therapeutic approach for the treatment of aseptic prosthesis loosening.