Biomedical Science and Technology Lab, IRCCS Istituto Ortopedico Rizzoli, via di Barbiano 1/10, 40136 Bologna, Italy.
Laboratory of Nanobiotechnology, IRCCS Istituto Ortopedico Rizzoli, via di Barbiano 1/10, 40136 Bologna, Italy.
Nutrients. 2020 Dec 9;12(12):3779. doi: 10.3390/nu12123779.
Chronic metabolic acidosis leads to bone-remodelling disorders based on excessive mineral matrix resorption and inhibition of bone formation, but also affects the homeostasis of citrate, which is an essential player in maintaining the acid-base balance and in driving the mineralisation process. This study aimed to investigate the impact of acidosis on the osteogenic properties of bone-forming cells and the effects of citrate supplementation in restoring the osteogenic features impaired by the acidic milieu. For this purpose, human mesenchymal stromal cells were cultured in an osteogenic medium and the extracellular matrix mineralisation was analysed at the micro- and nano-level, both in neutral and acidic conditions and after treatment with calcium citrate and potassium citrate. The acidic milieu significantly decreased the citrate release and hindered the organisation of the extracellular matrix, but the citrate supplementation increased collagen production and, particularly calcium citrate, promoted the mineralisation process. Moreover, the positive effect of citrate supplementation was observed also in the physiological microenvironment. This in vitro study proves that the mineral matrix organisation is influenced by citrate availability in the microenvironment surrounding bone-forming cells, thus providing a biological basis for using citrate-based supplements in the management of bone-remodelling disorders related to chronic low-grade acidosis.
慢性代谢性酸中毒会导致骨骼重塑障碍，这是由于过度的矿物质基质吸收和骨形成抑制所致，但也会影响柠檬酸的内稳平衡，柠檬酸是维持酸碱平衡和驱动矿物质化过程的重要参与者。本研究旨在探讨酸中毒对成骨细胞成骨特性的影响，以及补充柠檬酸在恢复酸性环境中受损的成骨特征方面的作用。为此，将人骨髓基质细胞在成骨培养基中培养，并在中性和酸性条件下以及在用柠檬酸钙和柠檬酸钾处理后，在微观和纳观水平上分析细胞外基质的矿化情况。酸性环境显著降低了柠檬酸的释放并阻碍了细胞外基质的组织，但柠檬酸的补充增加了胶原蛋白的产生，特别是柠檬酸钙，促进了矿物质化过程。此外，柠檬酸补充的积极作用在生理微环境中也观察到了。这项体外研究证明，细胞外基质的矿化组织受到成骨细胞周围微环境中柠檬酸可用性的影响，从而为在管理与慢性低度酸中毒相关的骨骼重塑障碍时使用基于柠檬酸的补充剂提供了生物学基础。
