Distinct Concentration-Dependent Molecular Pathways Regulate Bone Cell Responses to Cobalt and Chromium Exposure from Joint Replacement Prostheses

Abstract

Systemic cobalt (Co) and chromium (Cr) concentrations may be elevated in patients with metal joint replacement prostheses. Several studies have highlighted the detrimental effects of this exposure on bone cells in vitro, but the underlying mechanisms remain unclear. In this study, we use whole-genome microarrays to comprehensively assess gene expression in primary human osteoblasts, osteoclast precursors and mature resorbing osteoclasts following exposure to clinically relevant circulating versus local periprosthetic tissue concentrations of Co2+ and Cr3+ ions and CoCr nanoparticles. We also describe the gene expression response in osteoblasts on routinely used prosthesis surfaces in the presence of metal exposure. Our results suggest that systemic levels of metal exposure have no effect on osteoblasts, and primarily inhibit osteoclast differentiation and function via altering the focal adhesion and extracellular matrix interaction pathways. In contrast, periprosthetic levels of metal exposure inhibit both osteoblast and osteoclast activity by altering HIF-1α signaling and endocytic/cytoskeletal genes respectively, as well as increasing inflammatory signaling with mechanistic implications for adverse reactions to metal debris. Furthermore, we identify gene clusters and KEGG pathways for which the expression correlates with increasing Co2+:Cr3+ concentrations, and has the potential to serve as early markers of metal toxicity. Finally, our study provides a molecular basis for the improved clinical outcomes for hydroxyapatite-coated prostheses that elicit a pro-survival osteogenic gene signature compared to grit-blasted and plasma-sprayed titanium-coated surfaces in the presence of metal exposure.

Effect of Rehabilitation Nursing under the Guidance of the Health Action Process Approach Model on Perioperative Nursing Effect of Artificial Hip Arthroplasty: Effect on Promoting Quality of Life and Postoperative Rehabilitation

“…There are a variety of surgical treatments for hip fracture in the elderly, mainly internal fixation and artificial hip arthroplasty [ 9 ]. FNFs are often treated with artificial hip replacement, intertrochanteric fractures can be treated with artificial hip replacement or fixation, and subtrochanteric fractures are often treated with internal fixation.…”

“…In the face of the high prevalence rate of hip injury, ensuring the quality and safety of surgery, scientific perioperative management and actively promoting healthy behavior are the key to enhance the quality of medical service [ 9 ]. Therefore, in this study, the HAPA model is adopted to guide perioperative nursing of artificial hip replacement and to explore its application effect in clinical rehabilitation nursing of hip replacement from a novel point of view, so as to provide a new direction for the rapid rehabilitation of this kind of patients [ 10 ].…”

HIF-1α Regulates Bone Homeostasis and Angiogenesis, Participating in the Occurrence of Bone Metabolic Diseases

“…Co-doped HA significantly upregulates HIF-1α and VEGF in MG-63 cells, then promotes cell cycle progression and proliferation and induces osteocyte differentiation [ 190 ]. HA as a prosthesis coating triggers survival osteogenic gene signals, rescues the inhibition of osteoblasts and osteoclasts activity caused by Co 2+ and chromium (Cr) ions concentration elevation around the prosthesis through regulating the HIF-1α signal pathway and endocytic/cytoskeletal gene [ 191 ]. Co-doped BG scaffolds with different mesoporous or chemical modifications of the upregulation of VEGF, HIF-1α, and osteogenic genes in BMSCs, promote angiogenesis and osteogenic differentiation, as well as inhibit chondrogenic differentiation [ 86 , 192 , 193 ].…”

Cobalt-Doped Mesoporous Silica Coated Magnetic Nanoparticles Promoting Accelerated Bone Healing in Distraction Osteogenesis

“…16,17 At higher concentrations, Co2 + ions can reduce osteoclast cell numbers and resorption activity in vivo. 18 Co2+ ions affect the bone mesenchymal stem cells (BMSCs) through various pathways such as mediating the expression of transforming growth factor-beta (TGF-β) and genes associated with HIF-1 signalling. 18,19 Therefore, we speculated that Co-doped M-MSNs (Co-MMSNs) may exert a synergistic effect on osteogenic activity during DO and accelerate bone formation.…”