Unit of Endocrinology and Diabetes, Campus Bio-Medico University, Rome, Italy.
Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy.
J Clin Endocrinol Metab. 2019 Aug 1;104(8):3088-3096. doi: 10.1210/jc.2018-02216.
Irisin is a hormonelike molecule that is cleaved and secreted by an unknown protease from fibronectin type III domain-containing protein 5 (FNDC5). It ameliorates bone status and muscle atrophy and influences energy homeostasis. PTH exerts several metabolic effects that may interact with the effects of irisin.
To test the hypothesis that irisin and PTH mutually affect their biological action, we evaluated FNDC5 mRNA and protein expression in myotubes treated with PTH (1-34) and parathyroid hormone receptor (PTH-r) mRNA expression in osteoblasts treated with r-irisin. To confirm the in vivo impact of PTH on irisin, we compared irisin serum concentrations in postmenopausal women with primary hyperparathyroidism (PHPT) and control subjects.
C2C12 myotubes were treated with short-term and continuous 10-10 M teriparatide and MC3T3-E1 osteoblasts with 100 ng/mL r-irisin for 8 hours. In a cross-sectional open-label trial, we enrolled 26 postmenopausal women with PHPT and 31 age-/body mass index (BMI)‒matched control subjects without impairment of calcium/phosphate metabolism.
Teriparatide treatment on myotubes significantly downregulated FNDC5 expression by acting through its own receptor, which in turn activated Erk11/2 phosphorylation. r-Irisin led to a 50% downregulation of PTH-r mRNA expression compared with untreated cells (P < 0.001). Irisin was significantly lower in the PHPT group than in age-/BMI-matched controls (4.5 ± 1.1 vs 12 ± 5.2 µg/mL; P < 0.001). No significant correlation between irisin and bone mineral density or PTH was recorded in the PHPT group.
Preclinical findings suggest the existence of an interplay between PTH and irisin metabolism that seems to be confirmed by the significant reduction of irisin concentration in postmenopausal women with PHPT.
鸢尾素是一种激素样分子，由纤维连接蛋白 III 型结构域包含蛋白 5（FNDC5）上的一种未知蛋白酶切割和分泌。它可改善骨骼状态和肌肉萎缩，并影响能量平衡。甲状旁腺激素（PTH）发挥多种代谢作用，这些作用可能与鸢尾素的作用相互影响。
为了验证鸢尾素和 PTH 相互影响其生物学作用的假设，我们评估了用 PTH（1-34）处理的肌管中 FNDC5 mRNA 和蛋白的表达，以及用 r-鸢尾素处理的成骨细胞中甲状旁腺激素受体（PTH-r）mRNA 的表达。为了证实 PTH 对鸢尾素的体内影响，我们比较了原发性甲状旁腺功能亢进症（PHPT）和对照组绝经后妇女的血清鸢尾素浓度。
用短期和连续的 10-10 M 特立帕肽处理 C2C12 肌管，用 100ng/mL r-鸢尾素处理 MC3T3-E1 成骨细胞 8 小时。在一项横断面、开放标签试验中，我们招募了 26 名患有 PHPT 的绝经后妇女和 31 名年龄/体重指数（BMI）匹配且无钙/磷代谢受损的对照组。
特立帕肽作用于肌管，通过其自身受体显著下调 FNDC5 表达，从而激活 Erk11/2 磷酸化。与未处理的细胞相比，r-鸢尾素使 PTH-r mRNA 表达下调 50%（P <0.001）。与年龄/ BMI 匹配的对照组相比，PHPT 组的鸢尾素水平显著降低（4.5 ± 1.1 对 12 ± 5.2µg/mL；P <0.001）。在 PHPT 组中，未记录到鸢尾素与骨密度或 PTH 之间存在显著相关性。
临床前研究结果表明，PTH 和鸢尾素代谢之间存在相互作用，这一作用似乎被绝经后 PHPT 妇女中鸢尾素浓度的显著降低所证实。
