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
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...
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2025-02-01
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| author | Kilian Roth Johannes Dominikus Pallua Gerald Degenhart Tobias De Zordo Christian Kremser Christian Reif Werner Streif Michael Schirmer |
| author_facet | Kilian Roth Johannes Dominikus Pallua Gerald Degenhart Tobias De Zordo Christian Kremser Christian Reif Werner Streif Michael Schirmer |
| author_sort | Kilian Roth |
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| description | 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. |
| format | Article |
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| institution | DOAJ |
| issn | 2218-273X |
| language | English |
| publishDate | 2025-02-01 |
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| spelling | doaj-art-8d4b35d702c04548b682f90c28a398822025-08-20T03:12:08ZengMDPI AGBiomolecules2218-273X2025-02-0115223910.3390/biom15020239Reduced Bone Quality of Sacrum and Lumbal Vertebrae Spongiosa in Toll-like Receptor 2- and Toll-like Receptor 4-Knockout Mice: A Blinded Micro-Computerized AnalysisKilian Roth0Johannes Dominikus Pallua1Gerald Degenhart2Tobias De Zordo3Christian Kremser4Christian Reif5Werner Streif6Michael Schirmer7Department of Internal Medicine, Medical University of Innsbruck, 6020 Innsbruck, AustriaCore Facility of MicroCT, Clinic for Orthopedics and Traumatology, Medical University of Innsbruck, 6020 Innsbruck, AustriaCore Facility of MicroCT, University Clinic for Radiology, Anichstraße 35, 6020 Innsbruck, AustriaDepartment of Radiology, Medical University of Innsbruck, 6020 Innsbruck, AustriaDepartment of Radiology, Medical University of Innsbruck, 6020 Innsbruck, AustriaDepartment of Pediatrics I, Medical University of Innsbruck, 6020 Innsbruck, AustriaDepartment of Pediatrics I, Medical University of Innsbruck, 6020 Innsbruck, AustriaDepartment of Internal Medicine, Medical University of Innsbruck, 6020 Innsbruck, AustriaToll-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.https://www.mdpi.com/2218-273X/15/2/239toll-like receptorsmicro-computed tomographybone microarchitecturespondyloarthritisbone remodelingosteoclastogenesis |
| spellingShingle | Kilian Roth Johannes Dominikus Pallua Gerald Degenhart Tobias De Zordo Christian Kremser Christian Reif Werner Streif Michael Schirmer 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 toll-like receptors micro-computed tomography bone microarchitecture spondyloarthritis bone remodeling osteoclastogenesis |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | toll-like receptors micro-computed tomography bone microarchitecture spondyloarthritis bone remodeling osteoclastogenesis |
| url | https://www.mdpi.com/2218-273X/15/2/239 |
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