Musculoskeletal Pathology Group, Health Research Institute of Santiago de Compostela (IDIS), Santiago University Clinical Hospital, SERGAS, 15706 Santiago de Compostela, Spain.
Int J Mol Sci. 2023 Feb 20;24(4):4175. doi: 10.3390/ijms24044175.
It is well known that patients with attention deficit hyperactivity disorder treated with stimulants, such as methylphenidate hydrochloride (MPH), have reduced height and weight. Even though MPH has an anorexigenic effect, an additional impact of this drug on the growth plate cannot be discarded. In this study, we aimed to determine the cellular effect of MPH on an in vitro growth plate model. We tested the effects of MPH on the viability and proliferation of a prechondrogenic cell line via an MTT assay. In vitro differentiation of this cell line was performed, and cell differentiation was evaluated through the expression of cartilage- and bone-related genes as measured via RT-PCR. MPH did not alter the viability or proliferation of prechondrogenic cells. However, it reduced the expression of cartilage extracellular matrix-related genes (type II collagen and aggrecan) and increased the expression of genes involved in growth plate calcification (Runx2, type I collagen, and osteocalcin) at different phases of their differentiation process. Our results evidence that MPH upregulates genes associated with growth plate hypertrophic differentiation. This may induce premature closure of the growth plate, which would contribute to the growth retardation that has been described to be induced by this drug.
众所周知，接受兴奋剂治疗的注意缺陷多动障碍患者（如盐酸哌甲酯）会出现身高和体重降低的情况。尽管哌甲酯具有抑制食欲的作用，但不能排除这种药物对生长板的额外影响。在这项研究中，我们旨在确定 MPH 对体外生长板模型的细胞作用。我们通过 MTT 测定法测试了 MPH 对预成软骨细胞系活力和增殖的影响。通过 RT-PCR 检测软骨和骨相关基因的表达来评估该细胞系的体外分化。MPH 并未改变预成软骨细胞的活力或增殖。然而，它降低了软骨细胞外基质相关基因（II 型胶原和聚集蛋白聚糖）的表达，同时增加了生长板钙化相关基因（Runx2、I 型胶原和骨钙素）在分化过程不同阶段的表达。我们的结果表明，MPH 上调了与生长板肥大分化相关的基因。这可能导致生长板过早闭合，从而导致这种药物引起的生长迟缓。
