Glucocorticoids Alter Bone Microvascular Barrier via MAPK/Connexin43 Mechanisms

Published

January 20, 2025

Author(s)

Eun Jin Lee, Peter Lialios, Micaila Curtis, James Williams IV, Yoontae Kim, Paul Salipante, Steven Hudson, Mandy Esch, moshe levi, Joanna Kitlinska, Stella Alimperti

Abstract

Glucocorticoids (GCs) are standard-of-care treatments for inflammatory and immune disorders, and their long-term use increases the risk of osteoporosis. Although GCs decrease bone functionality, their role in bone microvasculature is incompletely understood. Herein, the study investigates the mechanisms of bone microvascular barrier function via osteoblast-endothelial interactions in response to GCs. The animal data shows that prednisolone (Psl) downregulated the osteoblast function and microvessel number and size. To investigate the role of GCs in bone endothelial barrier function further, a bicellular microfluidic in vitro system is developed and utilized, which consists of three-dimensional (3D) perfusable microvascular structures embedded in collagen I/osteoblast matrix. Interestingly, it is demonstrated that GCs significantly inhibit osteogenesis and microvascular barrier function by interfering with endothelial-osteoblast interactions. This effect is triggered by MAPK-induced phosphorylation of connexin43 (Cx43) at Ser282. Collectively, this study sheds light on microvascular function in bone disorders, as osteoporosis, and permits to capture dynamic changes in endothelial-bone interactions under GCs by dissecting the MAPK/Cx43 mechanism and proposing this as a potential target for bone diseases.

Citation

Advanced Healthcare Materials

Pub Type

Journals

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https://doi.org/10.1002/adhm.202404302

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Keywords

3D bicellular platform, microfluidics, microvasculature, bone, Connexin43, glucocorticoids, osteoporosis

Citation

Lee, E. , Lialios, P. , Curtis, M. , Williams IV, J. , Kim, Y. , Salipante, P. , Hudson, S. , Esch, M. , levi, M. , Kitlinska, J. and Alimperti, S. (2025), Glucocorticoids Alter Bone Microvascular Barrier via MAPK/Connexin43 Mechanisms, Advanced Healthcare Materials, [online], https://doi.org/10.1002/adhm.202404302, https://tsapps.nist.gov/publication/get_pdf.cfm?pub_id=934818 (Accessed October 9, 2025)