Sex hormone-binding globulin promotes the osteogenic differentiation potential of equine adipose-derived stromal cells by activating the BMP signaling pathway

BackgroundMusculoskeletal injuries and chronic degenerative diseases pose significant challenges in equine health, impacting performance and overall well-being. Sex Hormone-Binding Globulin (SHBG) is a glycoprotein determining the bioavailability of sex hormones in the bloodstream, and exerting crit...

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Main Authors: Jennifer M. Irwin-Huston, Lynda Bourebaba, Nabila Bourebaba, Artur Tomal, Krzysztof Marycz
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-10-01
Series:Frontiers in Endocrinology
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Online Access:https://www.frontiersin.org/articles/10.3389/fendo.2024.1424873/full
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author Jennifer M. Irwin-Huston
Lynda Bourebaba
Nabila Bourebaba
Artur Tomal
Krzysztof Marycz
Krzysztof Marycz
Krzysztof Marycz
author_facet Jennifer M. Irwin-Huston
Lynda Bourebaba
Nabila Bourebaba
Artur Tomal
Krzysztof Marycz
Krzysztof Marycz
Krzysztof Marycz
author_sort Jennifer M. Irwin-Huston
collection DOAJ
description BackgroundMusculoskeletal injuries and chronic degenerative diseases pose significant challenges in equine health, impacting performance and overall well-being. Sex Hormone-Binding Globulin (SHBG) is a glycoprotein determining the bioavailability of sex hormones in the bloodstream, and exerting critical metabolic functions, thus impacting the homeostasis of many tissues including the bone.MethodsIn this study, we investigated the potential role of SHBG in promoting osteogenesis and its underlying mechanisms in a model of equine adipose-derived stromal cells (ASCs). An SHBG-knocked down model has been established using predesigned siRNA, and cells subjected to osteogenic induction medium in the presence of exogenous SHBG protein. Changes in differentiation events where then screened using various analytical methods.ResultsWe demonstrated that SHBG treatment enhances the expression of key osteoconductive regulators in equine ASCs CD34+ cells, suggesting its therapeutic potential for bone regeneration. Specifically, SHBG increased the cellular expression of BMP2/4, osteocalcin (OCL), alkaline phosphatase (ALP), and osteopontin (OPN), crucial factors in early osteogenesis. Furthermore, SHBG treatment maintained adequate apoptosis and enhanced autophagy during osteogenic differentiation, contributing to bone formation and remodeling. SHBG further targeted mitochondrial dynamics, and promoted the reorganization of the mitochondrial network, as well as the expression of dynamics mediators including PINK, PARKIN and MFN1, suggesting its role in adapting cells to the osteogenic milieu, with implications for osteoblast maturation and differentiation.ConclusionOverall, our findings provide novel insights into SHBG’s role in bone formation and suggest its potential therapeutic utility for bone regeneration in equine medicine.
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spelling doaj-art-50b817f1e6ec4cb2bec150d7039fc56b2025-08-20T02:17:02ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922024-10-011510.3389/fendo.2024.14248731424873Sex hormone-binding globulin promotes the osteogenic differentiation potential of equine adipose-derived stromal cells by activating the BMP signaling pathwayJennifer M. Irwin-Huston0Lynda Bourebaba1Nabila Bourebaba2Artur Tomal3Krzysztof Marycz4Krzysztof Marycz5Krzysztof Marycz6Department of Experimental Biology, Faculty of Biology and Animal Science, Wrocław University of Environmental and Life Sciences, Wrocław, PolandDepartment of Experimental Biology, Faculty of Biology and Animal Science, Wrocław University of Environmental and Life Sciences, Wrocław, PolandDepartment of Experimental Biology, Faculty of Biology and Animal Science, Wrocław University of Environmental and Life Sciences, Wrocław, PolandInternational Institute of Translational Medicine, Wisznia Mała, PolandDepartment of Experimental Biology, Faculty of Biology and Animal Science, Wrocław University of Environmental and Life Sciences, Wrocław, PolandInternational Institute of Translational Medicine, Wisznia Mała, PolandDepartment of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, Davis, CA, United StatesBackgroundMusculoskeletal injuries and chronic degenerative diseases pose significant challenges in equine health, impacting performance and overall well-being. Sex Hormone-Binding Globulin (SHBG) is a glycoprotein determining the bioavailability of sex hormones in the bloodstream, and exerting critical metabolic functions, thus impacting the homeostasis of many tissues including the bone.MethodsIn this study, we investigated the potential role of SHBG in promoting osteogenesis and its underlying mechanisms in a model of equine adipose-derived stromal cells (ASCs). An SHBG-knocked down model has been established using predesigned siRNA, and cells subjected to osteogenic induction medium in the presence of exogenous SHBG protein. Changes in differentiation events where then screened using various analytical methods.ResultsWe demonstrated that SHBG treatment enhances the expression of key osteoconductive regulators in equine ASCs CD34+ cells, suggesting its therapeutic potential for bone regeneration. Specifically, SHBG increased the cellular expression of BMP2/4, osteocalcin (OCL), alkaline phosphatase (ALP), and osteopontin (OPN), crucial factors in early osteogenesis. Furthermore, SHBG treatment maintained adequate apoptosis and enhanced autophagy during osteogenic differentiation, contributing to bone formation and remodeling. SHBG further targeted mitochondrial dynamics, and promoted the reorganization of the mitochondrial network, as well as the expression of dynamics mediators including PINK, PARKIN and MFN1, suggesting its role in adapting cells to the osteogenic milieu, with implications for osteoblast maturation and differentiation.ConclusionOverall, our findings provide novel insights into SHBG’s role in bone formation and suggest its potential therapeutic utility for bone regeneration in equine medicine.https://www.frontiersin.org/articles/10.3389/fendo.2024.1424873/fullosteogenesisASCsSHBGBMPmitochondrial dynamicsautophagy
spellingShingle Jennifer M. Irwin-Huston
Lynda Bourebaba
Nabila Bourebaba
Artur Tomal
Krzysztof Marycz
Krzysztof Marycz
Krzysztof Marycz
Sex hormone-binding globulin promotes the osteogenic differentiation potential of equine adipose-derived stromal cells by activating the BMP signaling pathway
Frontiers in Endocrinology
osteogenesis
ASCs
SHBG
BMP
mitochondrial dynamics
autophagy
title Sex hormone-binding globulin promotes the osteogenic differentiation potential of equine adipose-derived stromal cells by activating the BMP signaling pathway
title_full Sex hormone-binding globulin promotes the osteogenic differentiation potential of equine adipose-derived stromal cells by activating the BMP signaling pathway
title_fullStr Sex hormone-binding globulin promotes the osteogenic differentiation potential of equine adipose-derived stromal cells by activating the BMP signaling pathway
title_full_unstemmed Sex hormone-binding globulin promotes the osteogenic differentiation potential of equine adipose-derived stromal cells by activating the BMP signaling pathway
title_short Sex hormone-binding globulin promotes the osteogenic differentiation potential of equine adipose-derived stromal cells by activating the BMP signaling pathway
title_sort sex hormone binding globulin promotes the osteogenic differentiation potential of equine adipose derived stromal cells by activating the bmp signaling pathway
topic osteogenesis
ASCs
SHBG
BMP
mitochondrial dynamics
autophagy
url https://www.frontiersin.org/articles/10.3389/fendo.2024.1424873/full
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