Impacto da Inibição de Janus Quinase com Tofacitinib nos Processos Fundamentais de Regeneração Óssea
TOF demonstrated a dose-dependent promotion of human mesenchymal stromal cell (hMSC) recruitment under hypoxia, while inhibiting recruitment under normoxia. TOF also
dose-dependently enhances osteogenic differentiation of hMSCs and reduces osteoclast differentiation and activity.
As people age, they are more likely to suffer from fractures and delayed bone healing, as well as degenerative joint diseases or osteoporosis. Bone metabolism and fracture healing may be negatively affected by underlying inflammatory disease, as well as anti-inflammatory treatment with glucocorticoids or NSAIDs.
JAK inhibition has demonstrated potent anti-inflammatory effects, but its impact on the fundamental processes of bone regeneration remains elusive. This study aimed to examine the effect of TOF on bone healing, with a focus on recruitment of hMSCs, chondrogenesis, osteogenesis, and osteoclastogenesis.
The results demonstrated that both dose and environmental oxygen levels determine the effects of TOF on hMSC recruitment. Dose-dependent effects were also seen for osteogenic differentiation and osteoclast differentiation and activity. The authors concluded that TOF may influence bone healing by promotion of hMSC recruitment into the hypoxic microenvironment of the fracture gap, but it does not interfere with the soft callus phase. They further hypothesise that there is no need to stop TOF in case of fracture, and that positive effects on osteoporosis are likely.