College of Medicine, Shaoxing University, Shaoxing, People's Republic of China.
Microsc Res Tech. 2022 Nov;85(11):3608-3617. doi: 10.1002/jemt.24213. Epub 2022 Jul 25.
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.
锌（Zn）是一种必需的微量元素，能刺激骨形成并抑制破骨细胞的骨吸收，从而控制骨的生长和维持。然而，锌补充对磷酸三钙（TCP）磨损颗粒诱导的溶骨作用的影响尚不清楚。在这里，我们将锌掺杂到 TCP 颗粒中（ZnTCP），并探讨锌对体内 TCP 颗粒诱导的溶骨性的保护作用。将 TCP 颗粒和 ZnTCP 颗粒包埋在小鼠颅骨中缝周围的骨膜下。2 周后，收集血液、骨膜组织和颅骨，以确定血清中 Zn 和骨钙素的水平、促炎细胞因子、骨生化标志物、破骨细胞生成和骨吸收面积，并解释其机制。数据表明，Zn 可显著预防 TCP 颗粒诱导的破骨细胞生成和骨丢失，并增加骨转换。Zn 补充剂显著抑制促炎细胞因子如肿瘤坏死因子（TNF）-α、白细胞介素（IL）-1β和 IL-6 的释放。免疫印迹表明，Zn 减轻了葡萄糖调节蛋白 78（GRP78）、PKR 样内质网激酶（PERK）、磷酸化 PERK（p-PERK）、真核起始因子 2α（eIF2α）、磷酸化 eIF2α（p-eIF2α）、激活转录因子 4（ATF4）、肌醇需求酶 1α（IRE1-α）和 X 盒结合蛋白剪接（XBP1s）等内质网应激相关蛋白的表达水平，导致 p-PERK/PERK 和 p-eIF2α/eIF2α 的比值降低。综上所述，Zn 补充通过抑制内质网应激途径强烈预防 TCP 颗粒诱导的假体周围溶骨，这可能是治疗无菌性假体松动的一种新的治疗方法。
