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Updated: Jul 4, 2026
Methods to Enable Spatial Transcriptomics of Bone Tissues
Published on: May 3, 2024
Identification of novel bone-specific molecular targets of binge alcohol and ibandronate by transcriptome analysis
Ryan Himes1, Frederick H Wezeman, John J Callaci
1Department of Orthopaedic Surgery and Rehabilitation, Loyola University Stritch School of Medicine, Maywood, Illinois 60153, USA.
Background:
Our laboratory established that binge alcohol-related bone damage is prevented by aminobisphosphonates, suggesting bone resorption increases following binge exposure. We examined the effects of binge alcohol and antiresorptive therapy on the relationship between bone damage and modulation of the vertebral transcriptome, in an attempt to determine how alcohol-induced bone damage and its prevention modulate bone-related biological pathways.
Methods:
Male Sprague-Dawley rats were assigned to 1 of 6 treatment groups (n = 12/group). (C1) saline ip 3 d/wk for 1 week, (A1) binge alcohol, 3 g/kg, ip 3 d/wk for 1 week, (C4) saline ip, 3 d/wk for 4 weeks, (A4) binge alcohol, ip, 3 g/kg 3 d/wk for 4 weeks, (I4) ibandronate, saline ip 3 d/wk for 4 weeks, plus a single ip injection of ibandronate at 120 microg/animal, and (AI4) binge alcohol plus ibandronate as above. After 1 or 4 weeks, adjacent lumbar vertebrae were assayed for bone damage or transcriptional changes.
Results:
Bone loss was not observed after 1 week of binge alcohol treatment. After 4 weeks, binge alcohol decreased vertebral BMD by 23% (p < 0.05) and compressive strength by 18% compared to saline controls (p < 0.05). Concurrent ibandronate prevented bone loss, increasing these parameters by 145 and 134% respectively compared to binge alcohol. (p < 0.05). Analysis of the vertebral transcriptome identified gene clusters specific for acute and chronic binge alcohol-related bone damage. Acute binge alcohol modulated the expression of integrin signaling-specific genes, while chronic binge alcohol modulated canonical Wnt signaling gene expression. Ibandronate normalized the expression of approximately 20% of the genes affected by chronic binge alcohol, allowing the identification of a unique subset of alcohol-sensitive, ibandronate-responsive genes.
Conclusions:
Identification of bone-specific gene expression clusters associated with acute and chronic binge alcohol treatment allowed for the identification of cellular pathways affected by binge treatment with known involvement in bone remodeling (Integrin, Canonical Wnt signaling) not previously identified as alcohol-sensitive. This data provides a basis for a plausible mechanistic explanation for the known detrimental effects of alcohol on bone formation and resorption.
Insights
Binge alcohol consumption causes bone damage by altering gene expression in vertebrae. Antiresorptive therapy with ibandronate prevents this bone loss and normalizes some alcohol-affected gene pathways.
Area of Science:
- Bone biology and toxicology
- Pharmacology and molecular pathways
Background:
- Binge alcohol consumption is linked to bone damage, suggesting increased bone resorption.
- Aminobisphosphonates prevent alcohol-related bone damage, indicating their therapeutic potential.
Purpose of the Study:
- To investigate the effects of binge alcohol and antiresorptive therapy on vertebral bone damage.
- To identify molecular pathways modulated by alcohol-induced bone damage and its prevention.
Main Methods:
- Male Sprague-Dawley rats were subjected to binge alcohol (3 g/kg) or saline for 1 or 4 weeks.
- Some groups received concurrent ibandronate treatment.
- Vertebrae were analyzed for bone mineral density (BMD), compressive strength, and transcriptional changes.
Main Results:
- Four weeks of binge alcohol decreased vertebral BMD by 23% and compressive strength by 18%.
- Ibandronate prevented alcohol-induced bone loss and normalized BMD and strength.
- Transcriptome analysis revealed alcohol-modulated gene expression in integrin and Wnt signaling pathways.
Conclusions:
- Binge alcohol affects bone remodeling through integrin and Wnt signaling pathways.
- Ibandronate normalizes a subset of alcohol-sensitive genes, offering a mechanistic explanation for its protective effects.
- This study identifies novel alcohol-sensitive pathways involved in bone remodeling.