| Autor: |
Megan B. Kuhn, Hayden S. VandenBerg, Andrew J. Reynolds, Matthew D. Carson, Amy J. Warner, Amanda C. LaRue, Chad M. Novince, Jessica D. Hathaway-Schrader |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
|
| Zdroj: |
Bone Reports, Vol 18, Iss , Pp 101662- (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2352-1872 |
| DOI: |
10.1016/j.bonr.2023.101662 |
| Popis: |
Osteoimmune studies have identified complement signaling as an important regulator of the skeleton. Specifically, complement anaphylatoxin receptors (i.e., C3aR, C5aR) are expressed on osteoblasts and osteoclasts, implying that C3a and/or C5a may be candidate mediators of skeletal homeostasis. The study aimed to determine how complement signaling influences bone modeling/remodeling in the young skeleton. Female C57BL/6J C3aR−/-C5aR−/− vs. wildtype and C3aR−/− vs. wildtype mice were examined at age 10 weeks. Trabecular and cortical bone parameters were analyzed by micro-CT. In situ osteoblast and osteoclast outcomes were determined by histomorphometry. Osteoblast and osteoclast precursors were assessed in vitro. C3aR−/-C5aR−/− mice displayed an increased trabecular bone phenotype at age 10 weeks. In vitro studies revealed C3aR−/-C5aR−/− vs. wildtype cultures had less bone-resorbing osteoclasts and increased bone-forming osteoblasts, which were validated in vivo. To determine whether C3aR alone was critical for the enhanced skeletal outcomes, wildtype vs. C3aR−/− mice were evaluated for osseous tissue outcomes. Paralleling skeletal findings in C3aR−/-C5aR−/− mice, C3aR−/− vs. wildtype mice had an enhanced trabecular bone volume fraction, which was attributed to increased trabecular number. There was elevated osteoblast activity and suppressed osteoclastic cells in C3aR−/− vs. wildtype mice. Furthermore, primary osteoblasts derived from wildtype mice were stimulated with exogenous C3a, which more profoundly upregulated C3ar1 and the pro-osteoclastic chemokine Cxcl1. This study introduces the C3a/C3aR signaling axis as a novel regulator of the young skeleton. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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