Michalowska M, Znorko B, Kaminski T, Oksztulska-Kolanek E, Pawlak D
Department of Pharmacodynamics, Medical University of Bialystok, Bialystok, Poland.
Department of Monitored Pharmacotherapy, Medical University of Bialystok, Bialystok, Poland.
J Physiol Pharmacol. 2015 Dec;66(6):779-91.
Osteoporosis, a debilitating disease caused by an imbalance between the action of osteoblasts and osteoclasts, is becoming an increasing problem in today's aging population. Although many advances in this field have addressed certain aspects of disease progression and pain management, new approaches to treatment are required. This review focuses on the influence of tryptophan, its metabolites and their influence on bone remodeling. Tryptophan is a precursor to serotonin, melatonin, kynurenines and niacin. Changes of tryptophan levels were noticed in bone metabolic diseases. Moreover, some works indicate that tryptophan plays a role in osteoblastic differentiation. Serotonin can exert different effects on bones, which depend on site of serotonin synthesis. Gut-derived serotonin inhibits bone formation, whereas brain-derived serotonin enhances bone formation and decreases bone resorption. Melatonin, increased differentiation of human mesenchymal stem cells into the osteoblastic cell lineage. Results of melatonin action on bone are anabolic and antiresorptive. Activation of the second tryptophan metabolic pathway, the kynurenine pathway, is associated with osteoblastogenesis and can be implicated in the occurrence of bone diseases. Oxidation products like kynurenine stopped proliferation of bone marrow mesenchymal stem cells. This may result in inhibition of osteoblastic proliferation and differentiation. Kynurenic acid acts as an antagonist at glutamate receptors, which are expressed on osteoclasts. Quinolinic acid activates N-methyl-D-aspartate receptors. 3-hydroxyanthranilic acid exhibits pro-oxidant and antioxidant activity. Decreased concentration of 3-hydroxyanthranilic acid can be one of the causes of osteoporosis. 3-hydroxykynurenine reduced the viability of osteoblast-like cells. Picolinic acid exerted osteogenic effect in vitro. Kynurenine derivatives exert various effects on bones. Discovery of the exact mechanism of action of tryptophan metabolites on bones may take us a step closer to understanding the complicated mechanism of bone metabolism, which in turn may result in finding a new, effective therapy for treating bone diseases.
骨质疏松症是一种由成骨细胞和破骨细胞作用失衡引起的衰弱性疾病，在当今老龄化人口中已成为一个日益严重的问题。尽管该领域的许多进展已涉及疾病进展和疼痛管理的某些方面，但仍需要新的治疗方法。本综述重点关注色氨酸及其代谢产物的影响以及它们对骨重塑的影响。色氨酸是血清素、褪黑素、犬尿氨酸和烟酸的前体。在骨代谢疾病中已注意到色氨酸水平的变化。此外，一些研究表明色氨酸在成骨细胞分化中起作用。血清素可对骨骼产生不同影响，这取决于血清素合成的部位。肠道来源的血清素抑制骨形成，而脑来源的血清素增强骨形成并减少骨吸收。褪黑素可增加人间充质干细胞向成骨细胞谱系的分化。褪黑素对骨骼的作用结果是合成代谢和抗吸收的。色氨酸的第二条代谢途径即犬尿氨酸途径的激活与成骨细胞生成有关，并且可能与骨疾病的发生有关。犬尿氨酸等氧化产物会阻止骨髓间充质干细胞的增殖。这可能导致成骨细胞增殖和分化受到抑制。犬尿酸作为谷氨酸受体的拮抗剂，而谷氨酸受体在破骨细胞上表达。喹啉酸激活N-甲基-D-天冬氨酸受体。3-羟基邻氨基苯甲酸具有促氧化和抗氧化活性。3-羟基邻氨基苯甲酸浓度降低可能是骨质疏松症的原因之一。3-羟基犬尿氨酸降低了成骨样细胞的活力。吡啶甲酸在体外发挥成骨作用。犬尿氨酸衍生物对骨骼有多种影响。发现色氨酸代谢产物对骨骼的确切作用机制可能会使我们更接近理解骨代谢的复杂机制，进而可能找到一种新的、有效的骨疾病治疗方法。
