Evaluation of impaired growth plate development of long bones in skeletally immature mice by antirheumatic agents.

Autor: Caron MMJ; Department of Orthopaedic Surgery, CAPHRI Care and Public Health Research Institute, Maastricht University Medical Center, Maastricht, The Netherlands., van Rietbergen B; Department of Orthopaedic Surgery, CAPHRI Care and Public Health Research Institute, Maastricht University Medical Center, Maastricht, The Netherlands.; Orthopaedic Biomechanics, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands., Castermans TMR, Haartmans MJJ; Department of Orthopaedic Surgery, CAPHRI Care and Public Health Research Institute, Maastricht University Medical Center, Maastricht, The Netherlands., van Rhijn LW; Department of Orthopaedic Surgery, CAPHRI Care and Public Health Research Institute, Maastricht University Medical Center, Maastricht, The Netherlands., Welting TJM; Department of Orthopaedic Surgery, CAPHRI Care and Public Health Research Institute, Maastricht University Medical Center, Maastricht, The Netherlands., Witlox AMA; Department of Orthopaedic Surgery, CAPHRI Care and Public Health Research Institute, Maastricht University Medical Center, Maastricht, The Netherlands.
Jazyk: angličtina
Zdroj: Journal of orthopaedic research : official publication of the Orthopaedic Research Society [J Orthop Res] 2021 Mar; Vol. 39 (3), pp. 553-564. Date of Electronic Publication: 2020 Aug 11.
DOI: 10.1002/jor.24819
Abstrakt: Restriction of physical growth and development is a known problem in patients with juvenile idiopathic arthritis (JIA). However, the effect of medical treatment for JIA on skeletal growth in affected children has not been properly investigated. We, therefore, hypothesize that naproxen and methotrexate (MTX) affect endochondral ossification and will lead to reduced skeletal development. Treatment of ATDC5 cells, an in vitro model for endochondral ossification, with naproxen or MTX resulted in increased chondrogenic but decreased hypertrophic differentiation. In vivo, healthy growing C57BL/6 mice were treated with naproxen, MTX, or placebo for 10 weeks. At 15 weeks postnatal, both the length of the tibia and the length of the femur were significantly reduced in the naproxen- and MTX-treated mice compared to their controls. Growth plate analysis revealed a significantly thicker proliferative zone, while the hypertrophic zone was significantly thinner in both experimental groups compared to their controls, comparable to the in vitro results. Micro-computed tomography analysis of the subchondral bone region directly below the growth disc showed significantly altered bone microarchitecture in naproxen and MTX groups. In addition, the involvement of the PTHrP-Ihh loop in naproxen- and MTX-treated cells was shown. Overall, these results demonstrate that naproxen and MTX have a profound effect on endochondral ossification during growth plate development, abnormal subchondral bone morphology, and reduced bone length. A better understanding of how medication influences the development of the growth plate will improve understanding of endochondral ossification and reveal possibilities to improve the treatment of pediatric patients.
(© 2020 The Authors. Journal of Orthopaedic Research ® published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.)
Databáze: MEDLINE
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