Catalytic Longevity Foundation, San Diego, CA 92109, USA.
Department of Research and Postgraduate in Food Science, Sonoran University, Hermosillo 83200, Mexico.
Int J Mol Sci. 2022 Apr 26;23(9):4776. doi: 10.3390/ijms23094776.
There is a vast pre-clinical literature suggesting that certain nutraceuticals have the potential to aid the preservation of bone mass in the context of estrogen withdrawal, glucocorticoid treatment, chronic inflammation, or aging. In an effort to bring some logical clarity to these findings, the signaling pathways regulating osteoblast, osteocyte, and osteoclast induction, activity, and survival are briefly reviewed in the present study. The focus is placed on the following factors: the mechanisms that induce and activate the RUNX2 transcription factor, a key driver of osteoblast differentiation and function; the promotion of autophagy and prevention of apoptosis in osteoblasts/osteoclasts; and the induction and activation of NFATc1, which promotes the expression of many proteins required for osteoclast-mediated osteolysis. This analysis suggests that the activation of sirtuin 1 (Sirt1), AMP-activated protein kinase (AMPK), the Nrf2 transcription factor, and soluble guanylate cyclase (sGC) can be expected to aid the maintenance of bone mass, whereas the inhibition of the serine kinase CK2 should also be protective in this regard. Fortuitously, nutraceuticals are available to address each of these targets. Sirt1 activation can be promoted with ferulic acid, N1-methylnicotinamide, melatonin, nicotinamide riboside, glucosamine, and thymoquinone. Berberine, such as the drug metformin, is a clinically useful activator of AMPK. Many agents, including lipoic acid, melatonin, thymoquinone, astaxanthin, and crucifera-derived sulforaphane, can promote Nrf2 activity. Pharmacological doses of biotin can directly stimulate sGC. Additionally, certain flavonols, notably quercetin, can inhibit CK2 in high nanomolar concentrations that may be clinically relevant. Many, though not all, of these agents have shown favorable effects on bone density and structure in rodent models of bone loss. Complex nutraceutical regimens providing a selection of these nutraceuticals in clinically meaningful doses may have an important potential for preserving bone health. Concurrent supplementation with taurine, N-acetylcysteine, vitamins D and K2, and minerals, including magnesium, zinc, and manganese, plus a diet naturally high in potassium, may also be helpful in this regard.
有大量的临床前文献表明，某些营养保健品具有在雌激素缺乏、糖皮质激素治疗、慢性炎症或衰老的情况下帮助维持骨量的潜力。为了使这些发现更加清晰，本研究简要回顾了调节成骨细胞、骨细胞和破骨细胞诱导、活性和存活的信号通路。重点放在以下因素上：诱导和激活 RUNX2 转录因子的机制，该转录因子是成骨细胞分化和功能的关键驱动因素；促进成骨细胞/破骨细胞自噬和预防细胞凋亡；诱导和激活 NFATc1，促进破骨细胞介导的骨溶解所需的许多蛋白质的表达。这一分析表明，激活 Sirtuin 1（Sirt1）、AMP 激活蛋白激酶（AMPK）、Nrf2 转录因子和可溶性鸟苷酸环化酶（sGC）有望有助于维持骨量，而抑制丝氨酸激酶 CK2 在这方面也具有保护作用。幸运的是，有营养保健品可用于解决这些问题。可用阿魏酸、N1-甲基烟酰胺、褪黑素、烟酰胺核苷、氨基葡萄糖和百里醌来促进 Sirt1 激活。像药物二甲双胍这样的小檗碱是一种临床有用的 AMPK 激活剂。许多药物，包括硫辛酸、褪黑素、百里醌、虾青素和十字花科蔬菜衍生的萝卜硫素，都可以促进 Nrf2 活性。生物素的药理剂量可以直接刺激 sGC。此外，某些类黄酮，特别是槲皮素，在可能具有临床意义的高纳摩尔浓度下可以抑制 CK2。许多（但不是全部）这些药物在骨丢失的啮齿动物模型中显示出对骨密度和结构的有利影响。提供这些营养保健品的选择并以临床相关剂量给予的复杂营养保健品方案可能对维持骨骼健康具有重要的潜力。同时补充牛磺酸、N-乙酰半胱氨酸、维生素 D 和 K2 以及矿物质，包括镁、锌和锰，加上富含钾的饮食，在这方面也可能有帮助。
