University of Oulu

Huovinen, J., Palosaari, S., Pesonen, P., Huhtakangas, J. A., & Lehenkari, P. (2023). 1,25(Oh)2D3 and its analogue calcipotriol inhibit the migration of human synovial and mesenchymal stromal cells in a wound healing model – A comparison with glucocorticoids. The Journal of Steroid Biochemistry and Molecular Biology, 233, 106373. https://doi.org/10.1016/j.jsbmb.2023.106373

1,25(OH)₂D₃ and its analogue calcipotriol inhibit the migration of human synovial and mesenchymal stromal cells in a wound healing model : a comparison with glucocorticoids

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Author: Huovinen, Jere1; Palosaari, Sanna1; Pesonen, Paula2;
Organizations: 1Research Unit of Translational Medicine, Medical Research Center Oulu, Oulu University Hospital and University of Oulu, P.O.Box 5000, FI-90014 Oulu, Finland
2Infrastructure for Population Studies, Faculty of Medicine, University of Oulu, Oulu, Finland
3Kuopio University Hospital, Division of Rheumatology, KYS, BOX 100, 70029 Kuopio, Finland
4Division of Operative Care, Oulu University Hospital and University of Oulu, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 4.5 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe20230927137633
Language: English
Published: Elsevier, 2023
Publish Date: 2023-09-27
Description:

Abstract

Vitamin D analogue calcipotriol is currently used in the local treatment of psoriasis. However, it also has antiproliferative and anti-inflammatory effects in the cells of the joint — suggesting a possible benefit in local treatment of arthritis. In this study, calcipotriol was studied in different in vitro methods to find out its effect on synovial and mesenchymal stromal cells. Primary human cell lines of osteoarthritis or rheumatoid arthritis patients (five mesenchymal stromal cells, MSC, and four synovial stromal cells, SSC) were cultured to study migration and proliferation of the cells in a wound healing model. The media was supplemented with calcipotriol, 1,25(OH)2D3, dexamethasone, betamethasone, methylprednisolone or control solution in 1–100 nM concentrations. To see possible toxic effects of calcipotriol, concentrations up to 10 µM in SSCs and MSCs were studied in apoptosis and necrosis assays in four cell lines. Calcipotriol and 1,25(OH)₂D₃, as well as the three glucocorticoids, reduced the migration of both SSCs and MSCs. In SSCs, the effect of calcipotriol and 1,25(OH)₂D₃ was at least as effective as with glucocorticoids, while with MSCs, the glucocorticoids were stronger inhibitors of migration. The antimigratory of calcipotriol and 1,25(OH)₂D₃ was consistently maintained in 10 µM and 1 µM. Calcipotriol was not toxic to MSCs and SSCs up to concentrations of 10 µM. Calcipotriol, as well as 1,25(OH)₂D₃, exerts antimigratory and antiproliferative effects on human SSCs and MSCs of the joint. These effects are not caused by apoptosis or necrosis. Both calcipotriol and 1,25(OH)₂D₃ have similar effects as glucocorticoids without apparent toxicity, suggesting that calcipotriol might be an eligible candidate to the local treatment of arthritis with a broad therapeutic window.

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Series: Journal of steroid biochemistry & molecular biology
ISSN: 0960-0760
ISSN-E: 1879-1220
ISSN-L: 0960-0760
Volume: 233
Article number: 106373
DOI: 10.1016/j.jsbmb.2023.106373
OADOI: https://oadoi.org/10.1016/j.jsbmb.2023.106373
Type of Publication: A1 Journal article – refereed
Field of Science: 1182 Biochemistry, cell and molecular biology
Subjects:
Funding: This study was funded by Finnish Medical Foundation, Sigrid Juselius Foundation, Northern Ostrobothnia Hospital District and the Finnish Society for Rheumatology.
Copyright information: © 2023 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
  https://creativecommons.org/licenses/by/4.0/