The enzyme soluble guanylate cyclase (sGC) plays an essential part in the nitric oxide (NO) signaling pathway by binding to the prosthetic heme group; thereby catalyzing the synthesis of cyclic guanosine monophosphate (cGMP)-dependent protein kinases. Impaired NO-sGC-cGMP signaling could lead to osteoblast apoptosis by mechanisms involving the oxidative-stress-induced shift of the redox state of the reduced heme to oxidized sGC, leading to diminished heme binding to the enzyme and rendering the sGC unresponsive to NO. Targeting oxidized sGC to enhance cGMP production could restore proliferation and differentiation of osteoblasts into osteocytes. Here, the potential role of sGC activators of an oxidized or heme-free sGC as a target for promoting osteoblast function is reviewed and strategies for delivering drugs to bone are identified.

中文翻译：

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靶向血红素氧化的可溶性鸟苷酸环化酶以促进成骨细胞功能。

可溶性可溶性鸟苷酸环化酶（sGC）通过与人工血红素基团结合，在一氧化氮（NO）信号传导途径中起着至关重要的作用。从而催化环状鸟苷单磷酸（cGMP）依赖性蛋白激酶的合成。受损的NO-sGC-cGMP信号传导可能通过涉及氧化应激诱导的还原血红素氧化还原状态转变为氧化sGC的机制而导致成骨细胞凋亡，从而导致血红素与酶的结合减少，并使sGC对NO无反应。靶向氧化的sGC以增强cGMP的产生可以恢复成骨细胞向骨细胞的增殖和分化。在此，对氧化或无血红素的sGC的sGC活化剂作为促进成骨细胞功能的靶标的潜在作用进行了综述，并确定了将药物递送至骨骼的策略。