Biomedical Orthopaedic Research Group, Centre for Orthopaedic & Trauma Research, The University of Adelaide, Adelaide, SA 5000, Australia.
Biomedical Orthopaedic Research Group, Centre for Orthopaedic & Trauma Research, The University of Adelaide, Adelaide, SA 5000, Australia; Orthopaedic and Trauma Service, Royal Adelaide Hospital, Adelaide, SA 5000, Australia.
Acta Biomater. 2019 Mar 15;87:296-306. doi: 10.1016/j.actbio.2019.01.047. Epub 2019 Jan 25.
Periprosthetic osteolysis is a major cause of implant failure in total hip replacements. Aseptic loosening caused by osteolytic lesions is associated with the production of bioactive wear particles from the articulations of implants. Wear particles infiltrate the surrounding tissue of implants, promoting inflammation as well as bone resorption. Osteocytes have been shown to both regulate physiological osteoclastogenesis and directly remodel their perilacunar bone matrix by the process of osteocytic osteolysis. We hypothesise that osteocytes respond to wear debris of orthopaedic implant materials by adopting a pro-catabolic phenotype and thus contribute to periprosthetic osteolysis through the known pathways of bone loss. Osteocyte responses to particles derived from clinically relevant materials, ultra-high molecular weight polyethylene (UHMWPE), highly cross-linked polyethylene (XLPE) and metal alloys, Ti6Al4V and CoCrMo, were examined in vitro in human primary osteocyte-like cultures. Osteocyte-like cells exposed to both polyethylene and metal wear particle types showed upregulated expression of catabolic markers associated with osteocytic osteolysis, MMP13, carbonic anhydrase 2 (CA2) and cathepsin K (CTSK). In addition, pro-osteoclastogenesis markers RANKL and M-CSF were induced, as well as the expression of pro-inflammatory cytokines, IL-6 and TNFα, albeit with different kinetics. These findings suggest a previously unrecognised action of wear particles of multiple orthopaedic materials on osteocytes, and suggest a multifaceted role for osteocytes in periprosthetic osteolysis. STATEMENT OF SIGNIFICANCE: This study addresses periprosthetic osteolysis, a major clinical problem leading to aseptic loosening of orthopaedic implants. It is well accepted that wear particles of polyethylene and of other implant materials stimulate the activity of bone resorbing osteoclasts. Our recent work provided evidence that commercial particles of ultra-high molecular weight polyethylene (UHMWPE) stimulated osteocytes to adopt a bone catabolic state. In this study we demonstrate for the first time that particles derived from materials in clinical use, conventional UHMWPE, highly cross-linked polyethylene (XLPE), and Ti6Al4V and CoCrMo metal alloys, all stimulate human osteocyte activities of osteocyte-regulated osteoclastogenesis, osteocytic osteolysis, proinflammatory responses, osteocyte apoptosis, albeit to varying extents. This study provides further mechanistic insight into orthopaedic wear particle mediated bone disease in terms of the osteocyte, the most abundant and key controlling cell type in bone.
假体周围骨溶解是全髋关节置换术假体失败的主要原因。由溶骨性病变引起的无菌性松动与来自植入物关节的生物活性磨损颗粒的产生有关。磨损颗粒渗透到植入物周围的组织中，促进炎症和骨吸收。已经表明，成骨细胞通过成骨细胞骨溶解过程来调节生理破骨细胞生成，并直接重塑其骨陷窝周围的骨基质。我们假设成骨细胞通过采用促分解代谢表型来响应骨科植入材料的磨损碎片，并通过已知的骨丢失途径导致假体周围骨溶解。在体外人原代成骨细胞样培养物中检查了源自临床相关材料（超高分子量聚乙烯（UHMWPE）、高度交联聚乙烯（XLPE）和金属合金（Ti6Al4V 和 CoCrMo）的成骨细胞对颗粒的反应。暴露于聚乙烯和金属磨损颗粒类型的成骨细胞样细胞表现出与成骨细胞骨溶解相关的分解代谢标志物的上调表达，MMP13、碳酸酐酶 2（CA2）和组织蛋白酶 K（CTSK）。此外，诱导了破骨细胞生成标志物 RANKL 和 M-CSF，以及促炎细胞因子 IL-6 和 TNFα 的表达，尽管具有不同的动力学。这些发现表明，多种骨科材料的磨损颗粒对成骨细胞具有先前未被认识到的作用，并表明成骨细胞在假体周围骨溶解中具有多方面的作用。意义声明：本研究解决了假体周围骨溶解的问题，这是导致骨科植入物无菌性松动的主要临床问题。众所周知，聚乙烯和其他植入材料的磨损颗粒会刺激破骨细胞的活性。我们最近的工作提供了证据，表明商业超高分子量聚乙烯（UHMWPE）颗粒刺激成骨细胞采用骨分解代谢状态。在这项研究中，我们首次证明，源自临床使用材料的颗粒，包括传统的 UHMWPE、高度交联聚乙烯（XLPE）以及 Ti6Al4V 和 CoCrMo 金属合金，均刺激人成骨细胞的成骨细胞调节的破骨细胞生成、成骨细胞骨溶解、促炎反应、成骨细胞凋亡，尽管程度不同。该研究提供了关于成骨细胞介导的骨科磨损颗粒介导的骨疾病的进一步机制见解，成骨细胞是骨中最丰富和关键的控制细胞类型。
