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Volume 15
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10.3390/biom15020239
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Article

Reduced Bone Quality of Sacrum and Lumbal Vertebrae Spongiosa in Toll-like Receptor 2- and Toll-like Receptor 4-Knockout Mice: A Blinded Micro-Computerized Analysis

by
Kilian Roth
1,†,
Johannes Dominikus Pallua
2,†,
Gerald Degenhart
3,
Tobias De Zordo
4,5,
Christian Kremser
4,
Christian Reif
6,
Werner Streif
6 and
Michael Schirmer
1,7,*
1
Department of Internal Medicine, Medical University of Innsbruck, 6020 Innsbruck, Austria
2
Core Facility of MicroCT, Clinic for Orthopedics and Traumatology, Medical University of Innsbruck, 6020 Innsbruck, Austria
3
Core Facility of MicroCT, University Clinic for Radiology, Anichstraße 35, 6020 Innsbruck, Austria
4
Department of Radiology, Medical University of Innsbruck, 6020 Innsbruck, Austria
5
Radiology Department, Brixsana Private Clinic, 39042 Brixen-Bressanone, Italy
6
Department of Pediatrics I, Medical University of Innsbruck, 6020 Innsbruck, Austria
7
Office for Internal Medicine/Rheumatology, 6060 Hall, Austria
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Biomolecules 2025, 15(2), 239; https://doi.org/10.3390/biom15020239
Submission received: 19 December 2024 / Revised: 23 January 2025 / Accepted: 31 January 2025 / Published: 7 February 2025
(This article belongs to the Special Issue Advances in the Molecular Mechanisms of Inflammatory Arthritis and Inflammation-Related Bone Changes)
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Abstract

Toll-like receptors (TLRs) are pivotal in modulating immune responses and have been implicated in bone remodeling. This in vivo study investigates the impact of TLR2 and TLR4 signaling on trabecular bone structure using micro-computed tomography in a murine model. Sacrum and lumbar vertebrae (L5, L6) from wildtype (WT), TLR2-knockout (TLR2-KO), and TLR4-knockout (TLR4-KO) mice were analyzed, with trabecular parameters such as connectivity density (Conn-Dens), trabecular thickness (DT-TbTh), and variability metrics (DT-Tb,(1/N),SD and DT-TbThSD) assessed. The results revealed significant differences among genotypes: TLR4-KO mice exhibited increased variability in trabecular distribution, indicating less stable bone structures, while TLR-KO mice showed lower variability in trabecular thickness, suggesting enhanced uniformity and robustness. BV/TV and 3D reconstructions highlighted lower bone volume fractions in the sacrum compared to lumbar vertebrae across genotypes, consistent with human observations of reduced sacral bone volume in spondyloarthritis (SpA). Interestingly, bone changes were independent of immunization-induced SpA, emphasizing a direct role in TLR signaling. These findings provide novel insights into the role of TLRs in bone microarchitecture and suggest implications for bone-related pathologies, particularly those involving inflammatory pathways. Future research may explore the translational relevance of TLR-mediated mechanisms in osteopenia and osteoporosis.
Keywords: toll-like receptors; micro-computed tomography; bone microarchitecture; spondyloarthritis; bone remodeling; osteoclastogenesis; infection toll-like receptors; micro-computed tomography; bone microarchitecture; spondyloarthritis; bone remodeling; osteoclastogenesis; infection

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MDPI and ACS Style

Roth, K.; Pallua, J.D.; Degenhart, G.; De Zordo, T.; Kremser, C.; Reif, C.; Streif, W.; Schirmer, M. Reduced Bone Quality of Sacrum and Lumbal Vertebrae Spongiosa in Toll-like Receptor 2- and Toll-like Receptor 4-Knockout Mice: A Blinded Micro-Computerized Analysis. Biomolecules 2025, 15, 239. https://doi.org/10.3390/biom15020239

AMA Style

Roth K, Pallua JD, Degenhart G, De Zordo T, Kremser C, Reif C, Streif W, Schirmer M. Reduced Bone Quality of Sacrum and Lumbal Vertebrae Spongiosa in Toll-like Receptor 2- and Toll-like Receptor 4-Knockout Mice: A Blinded Micro-Computerized Analysis. Biomolecules. 2025; 15(2):239. https://doi.org/10.3390/biom15020239

Chicago/Turabian Style

Roth, Kilian, Johannes Dominikus Pallua, Gerald Degenhart, Tobias De Zordo, Christian Kremser, Christian Reif, Werner Streif, and Michael Schirmer. 2025. "Reduced Bone Quality of Sacrum and Lumbal Vertebrae Spongiosa in Toll-like Receptor 2- and Toll-like Receptor 4-Knockout Mice: A Blinded Micro-Computerized Analysis" Biomolecules 15, no. 2: 239. https://doi.org/10.3390/biom15020239

APA Style

Roth, K., Pallua, J. D., Degenhart, G., De Zordo, T., Kremser, C., Reif, C., Streif, W., & Schirmer, M. (2025). Reduced Bone Quality of Sacrum and Lumbal Vertebrae Spongiosa in Toll-like Receptor 2- and Toll-like Receptor 4-Knockout Mice: A Blinded Micro-Computerized Analysis. Biomolecules, 15(2), 239. https://doi.org/10.3390/biom15020239

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