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Frontiers in endocrinology2024; 15; 1424873; doi: 10.3389/fendo.2024.1424873

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

Abstract: Musculoskeletal 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. Unassigned: In 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. Unassigned: We 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. Unassigned: Overall, our findings provide novel insights into SHBG's role in bone formation and suggest its potential therapeutic utility for bone regeneration in equine medicine.
Copyright © 2024 Irwin-Huston, Bourebaba, Bourebaba, Tomal and Marycz.
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Publication Date: 2024-10-17 PubMed ID: 39483986PubMed Central: PMC11524885DOI: 10.3389/fendo.2024.1424873Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This study investigates the role of Sex Hormone-Binding Globulin (SHBG) in promoting bone formation in horses, specifically through influencing the behaviour of equine adipose-derived stromal cells. The researchers found that SHBG enhances the activity of key factors in bone regeneration, providing promising insights into its potential use in treating skeletal injuries and chronic degenerative diseases in horses.

Study aim and methods

  • The primary goal of this research was to understand the influence of Sex Hormone-Binding Globulin (SHBG) on bone formation. SHBG is critical for the bioavailability of sex hormones and plays a significant role in the metabolic functions of several tissues, including bone.
  • To examine the potential role of SHBG in promoting osteogenesis (the process of bone formation), researchers used equine adipose-derived stromal cells (ASCs), cells derived from horse fat tissue that can differentiate into various types of cells, including bone cells.
  • An SHBG-knocked down model was established using predesigned siRNA. These cells were subjected to an osteogenic induction medium, which encourages the cells to differentiate into bone cells, in the presence of exogenous SHBG protein.
  • The researchers then used various analytical methods to screen changes in differentiation events resulting from the SHBG treatment.

Findings of the study

  • The results showed that SHBG treatment enhanced the expression of key osteoconductive regulators in equine ASCs CD34 cells, which indicate its potential value for bone regeneration.
  • Specifically, it increased the cellular expression of BMP2/4, osteocalcin (OCL), alkaline phosphatase (ALP), and osteopontin (OPN), all of which play crucial roles in the early stages of bone formation.
  • SHBG treatment maintained adequate apoptosis (which is a natural process of cell self-destruction) and enhanced autophagy (which is the process of cellular degradation and recycling) during osteogenic differentiation, contributing to bone formation and remodeling.
  • Furthermore, SHBG targeted mitochondrial dynamics and promoted the reorganization of the mitochondrial network, proposing its role in adapting cells to the osteogenic environment and implying implications for osteoblast maturation and differentiation.

Implications of the study

  • This study provides new insights into the role of SHBG in bone formation, suggesting a potential therapeutic use of SHBG for bone regeneration in equine medicine.
  • The findings suggest that SHBG could be utilised to treat musculoskeletal injuries and chronic degenerative diseases in horses, thereby enhancing their performance and overall well-being.

Cite This Article

APA
Irwin-Huston JM, Bourebaba L, Bourebaba N, Tomal A, Marycz K. (2024). Sex hormone-binding globulin promotes the osteogenic differentiation potential of equine adipose-derived stromal cells by activating the BMP signaling pathway. Front Endocrinol (Lausanne), 15, 1424873. https://doi.org/10.3389/fendo.2024.1424873

Publication

Frontiers in endocrinology
ISSN: 1664-2392
NlmUniqueID: 101555782
Country: Switzerland
Language: English
Volume: 15
Pages: 1424873
PII: 1424873

Researcher Affiliations

Irwin-Huston, Jennifer M
  • Department of Experimental Biology, Faculty of Biology and Animal Science, Wrocław University of Environmental and Life Sciences, Wrocław, Poland.
Bourebaba, Lynda
  • Department of Experimental Biology, Faculty of Biology and Animal Science, Wrocław University of Environmental and Life Sciences, Wrocław, Poland.
Bourebaba, Nabila
  • Department of Experimental Biology, Faculty of Biology and Animal Science, Wrocław University of Environmental and Life Sciences, Wrocław, Poland.
Tomal, Artur
  • International Institute of Translational Medicine, Wisznia Mała, Poland.
Marycz, Krzysztof
  • Department of Experimental Biology, Faculty of Biology and Animal Science, Wrocław University of Environmental and Life Sciences, Wrocław, Poland.
  • International Institute of Translational Medicine, Wisznia Mała, Poland.
  • Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, Davis, CA, United States.

MeSH Terms

  • Animals
  • Osteogenesis / drug effects
  • Horses
  • Cell Differentiation
  • Signal Transduction / drug effects
  • Sex Hormone-Binding Globulin / metabolism
  • Adipose Tissue / cytology
  • Adipose Tissue / metabolism
  • Mesenchymal Stem Cells / metabolism
  • Mesenchymal Stem Cells / cytology
  • Bone Morphogenetic Proteins / metabolism
  • Cells, Cultured
  • Stromal Cells / metabolism
  • Stromal Cells / cytology
  • Stromal Cells / drug effects
  • Osteoblasts / metabolism
  • Osteoblasts / cytology

Conflict of Interest Statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Citations

This article has been cited 2 times.
  1. Bourebaba N, Domagała J, Bourebaba L. Revitalizing equine metabolism: how SHBG improves mitochondrial function and reduces inflammation. BMC Vet Res 2025 Oct 21;21(1):620.
    doi: 10.1186/s12917-025-05033-ypubmed: 41121214google scholar: lookup
  2. Aeri A, Gorla M, Sharma GT. Veterinary Regenerative Medicine: The Evolving Role of Stem Cell-Based Therapies. Stem Cell Rev Rep 2025 Nov;21(8):2484-2510.
    doi: 10.1007/s12015-025-10963-zpubmed: 40900287google scholar: lookup
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