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Hypoxia\u2010inducible factor 1 (HIF\u20101) mediated signaling pathways, which normally modulate tissue metabolism under hypoxic circumstances, could be triggered by metallic wear debris and influence bone metabolism favoring osteolysis. This may lead to early loosening of the orthopedic implants. Immunhistochemical staining of periprosthetic tissues of failed artificial hip implants showed that the concentration of HIF\u20101\u03b1 in the surrounding tissues of failed MoM hip implants was significantly higher in comparison to failed metal\u2010on\u2010polyethylene (MoP) hip implants and osteoarthritic tissues. Therefore, we examined the Co<jats:sup>2+<\/jats:sup>\u2010uptake mechanisms and the influence of Co<jats:sup>2+<\/jats:sup> uptake on HIF\u20101\u03b1 stabilization. Based on cobalt mediated quenching effects, calcium imaging experiments using fura\u20102 showed a concentration\u2010dependent cobalt influx in MG\u201063 cells, which could be inhibited by the unspecific TRPM7 channel inhibitor 2\u2010APB (20 \u03bc<jats:italic>M<\/jats:italic>) and TRPM7 specific siRNA. Western blots confirmed a dose dependent increase of HIF\u20101\u03b1 upon stimulation with Co<jats:sup>2+<\/jats:sup>. This effect could be abrogated by inhibition of cobalt influx using 2\u2010APB. This study shows that chemical hypoxia originating from HIF\u20101\u03b1 upregulation within the periprosthetic tissue is related to cobalt wear debris and highlights TRPM7 as an important key mediator in this context. \u00a9 2018 Wiley Periodicals, Inc. 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