» Articles » PMID: 36835608

Methylphenidate Promotes Premature Growth Plate Closure: In Vitro Evidence

Overview
Journal Int J Mol Sci
Publisher MDPI
Date 2023 Feb 25
PMID 36835608
Authors
Affiliations
Soon will be listed here.
Abstract

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.

References
1.
Lian C, Wang X, Qiu X, Wu Z, Gao B, Liu L . Collagen type II suppresses articular chondrocyte hypertrophy and osteoarthritis progression by promoting integrin β1-SMAD1 interaction. Bone Res. 2019; 7:8. PMC: 6403405. DOI: 10.1038/s41413-019-0046-y. View

2.
Bliziotes M, McLoughlin S, GUNNESS M, Fumagalli F, Jones S, Caron M . Bone histomorphometric and biomechanical abnormalities in mice homozygous for deletion of the dopamine transporter gene. Bone. 2000; 26(1):15-9. DOI: 10.1016/s8756-3282(99)00232-x. View

3.
Danielson M, Bitsko R, Ghandour R, Holbrook J, Kogan M, Blumberg S . Prevalence of Parent-Reported ADHD Diagnosis and Associated Treatment Among U.S. Children and Adolescents, 2016. J Clin Child Adolesc Psychol. 2018; 47(2):199-212. PMC: 5834391. DOI: 10.1080/15374416.2017.1417860. View

4.
Greenhill L, Swanson J, Hechtman L, Waxmonsky J, Eugene Arnold L, Molina B . Trajectories of Growth Associated With Long-Term Stimulant Medication in the Multimodal Treatment Study of Attention-Deficit/Hyperactivity Disorder. J Am Acad Child Adolesc Psychiatry. 2019; 59(8):978-989. PMC: 7021562. DOI: 10.1016/j.jaac.2019.06.019. View

5.
Waxmonsky J, Pelham 3rd W, Campa A, Waschbusch D, Li T, Marshall R . A Randomized Controlled Trial of Interventions for Growth Suppression in Children With Attention-Deficit/Hyperactivity Disorder Treated With Central Nervous System Stimulants. J Am Acad Child Adolesc Psychiatry. 2019; 59(12):1330-1341. PMC: 7048642. DOI: 10.1016/j.jaac.2019.08.472. View