Pernow Ylva, Shahror Rami, Acharya Shikha, Jahnson Lena, Vumma Ravi, Venizelos Nikolaos
Department of Molecular Medicine and Surgery, Endocrine and Diabetes Unit, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
NGBI, Neuropsychiatric Research Laboratory, Faculty of Medicine and Health, School of Medical Sciences, Örebro University, SE 701 82 Örebro, Sweden.
Bone Rep. 2018 Jan 3;8:25-28. doi: 10.1016/j.bonr.2018.01.002. eCollection 2018 Jun.
It has been demonstrated, that long-term chronic tryptophan deficiency, results in decreased serotonin synthesis, which may lead to low bone mass and low bone formation. Findings from studies in male patients with idiopathic osteoporosis suggested a decreased transport of tryptophan in erythrocytes of osteoporotic patients, indicating that serotonin system defects may be involved in the etiology of low bone mass. Tryptophan is the precursor of serotonin, and a disturbed transport of tryptophan is implicated in altered serotonin synthesis. However, no study has investigated the tryptophan transport kinetics in MIO patients. The aim of this study is to investigate the kinetic parameters of tryptophan transport in fibroblasts derived from MIO patients compared to age and sex matched controls. Fibroblast cells were cultured from skin biopsies obtained from patients diagnosed with Male Idiopathic Osteoporosis and from healthy age-sex matched controls, without a diagnosis of osteoporosis. Transport of the amino acid tryptophan across the cell membrane was measured by the cluster tray method. The kinetic parameters, maximal transport capacity (V) and affinity constant (K) were determined by using the Lineweaver-Burke plot equation. The results of this study have shown a significantly lower mean value for V ( = 0.0138) and lower K mean value ( = 0.0009) of tryptophan transport in fibroblasts of MIO patients compared to the control group. A lower V implied a decreased tryptophan transport availability in MIO patients. In conclusion, reduced cellular tryptophan availability in MIO patients might result in reduced brain serotonin synthesis and its endogenous levels in peripheral tissues, and this may contribute to low bone mass/formation. The findings of the present study could contribute to the etiology of idiopathic osteoporosis and for the development of novel approaches for diagnosis, treatment and management strategies of MIO.
已经证明，长期慢性色氨酸缺乏会导致血清素合成减少，这可能会导致低骨量和低骨形成。对特发性骨质疏松症男性患者的研究结果表明，骨质疏松症患者红细胞中色氨酸的转运减少，这表明血清素系统缺陷可能参与了低骨量的病因。色氨酸是血清素的前体，色氨酸转运紊乱与血清素合成改变有关。然而，尚无研究调查男性特发性骨质疏松症（MIO）患者的色氨酸转运动力学。本研究的目的是调查与年龄和性别匹配的对照组相比，MIO患者来源的成纤维细胞中色氨酸转运的动力学参数。从诊断为男性特发性骨质疏松症的患者以及未诊断为骨质疏松症的年龄和性别匹配的健康对照者的皮肤活检中培养成纤维细胞。通过簇盘法测量氨基酸色氨酸跨细胞膜的转运。使用Lineweaver-Burke图方程确定动力学参数，即最大转运能力（V）和亲和常数（K）。本研究结果表明，与对照组相比，MIO患者成纤维细胞中色氨酸转运的V平均值（ = 0.0138）显著降低，K平均值（ = 0.0009）也较低。较低的V意味着MIO患者色氨酸转运可用性降低。总之，MIO患者细胞内色氨酸可用性降低可能导致大脑血清素合成减少及其在外周组织中的内源性水平降低，这可能导致低骨量/骨形成。本研究结果可能有助于特发性骨质疏松症的病因研究，并为MIO的诊断、治疗和管理策略的新方法开发做出贡献。
