ArticlePloS one2017
Osteoblast-specific overexpression of complement receptor C5aR1 impairs fracture healing.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 34 citations in OpenAlex.
- Trial
- Collectin-11 regulates osteoclastogenesis and bone maintenance via a complement-dependent mechanism.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Complement Proteins C1q-C5 as Context‑Dependent Regulators of Osteoblast Function and Fracture Healing: A Systematic Review.Orthopedic reviews · 2026Article
- Targeting innate immunity to modulate bone metabolism: a novel strategy for osteoporosis treatment.Frontiers in aging · 2026Review
- Physiologic impact of inflammation in the polytrauma patient.OTA international : the open access journal of orthopaedic trauma · 2025Article
- Investigating the role of complement 5a in systemic bone loss after myocardial infarction.Bone · 2025Article
- DAMPs, PAMPs, NLRs, RIGs, CLRs and TLRs - Understanding the Alphabet Soup in the Context of Bone Biology.Current osteoporosis reports · 2025Review
- Subchondral osteoclasts and osteoarthritis: new insights and potential therapeutic avenues.Acta biochimica et biophysica Sinica · 2024Review
- The heart-bone connection: relationships between myocardial infarction and osteoporotic fracture.American journal of physiology. Heart and circulatory physiology · 2024Review
- PLK3 promotes the proneural-mesenchymal transition in glioblastoma via transcriptional regulation of C5AR1.Molecular biology reports · 2023Article
- C3a-C3aR signaling is a novel modulator of skeletal homeostasis.Bone reports · 2023Article
- Altered early immune response after fracture and traumatic brain injury.Frontiers in immunology · 2023Article
- Topography-mediated immunomodulation in osseointegration; Ally or Enemy.Biomaterials · 2022Review
- The role of C5a-C5aR1 axis in bone pathophysiology: A mini-review.Frontiers in cell and developmental biology · 2022Review
- Mast Cells Drive Systemic Inflammation and Compromised Bone Repair After Trauma.Frontiers in immunology · 2022Article
- Complement receptor C5aR1 on osteoblasts regulates osteoclastogenesis in experimental postmenopausal osteoporosis.Frontiers in endocrinology · 2022Article
- Differences in Fracture Healing Between Female and Male C57BL/6J Mice.Frontiers in physiology · 2021Article
- By Increasing the Expression and Activation of STAT3, Sustained C5a Stimulation Increases the Proliferation, Migration, and Invasion of RCC Cells and Promotes the Growth of Transgrafted Tumors.Cancer management and research · 2021Article
- Systemic and Cardiac Alterations After Long Bone Fracture.Shock (Augusta, Ga.) · 2020Article
- Endochondral Bone Regeneration by Non-autologous Mesenchymal Stem Cells.Frontiers in bioengineering and biotechnology · 2020Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The anaphylatoxin receptor C5aR1 plays an important role not only in innate immune responses, but also in bone metabolism and fracture healing, being highly expressed on immune and bone cells, including osteoblasts and osteoclasts. C5aR1 induces osteoblast migration, cytokine generation and osteoclastogenesis, however, the exact role of C5aR1-mediated signaling in osteoblasts is not entirely known. Therefore, we hypothesized that osteoblasts are essential target cells for C5a and that fracture healing should be disturbed in mice with an osteoblast-specific C5aR1 overexpression (Col1a1-C5aR1). Osteoblast activity in vitro, bone phenotype and fracture healing after isolated osteotomy and after combined osteotomy with additional thoracic trauma were analyzed. The systemic and local inflammatory reactions were analyzed by determining C5a and IL-6 concentrations in blood, bronchoalveolar lavage fluid and fracture callus and the recruitment of immune cells. In vitro, osteoblast proliferation and differentiation were similar to wildtype cells, and phosphorylation of p38 and expression of IL-6 and RANKL were increased in osteoblasts derived from Col1a1-C5aR1 mice. Bone phenotype and the inflammatory reaction were unaffected in Col1a1-C5aR1 mice. Fracture healing was significantly impaired as demonstrated by significantly reduced bone content, bone mineral density and flexural rigidity, possibly due to significantly increased osteoclast numbers. C5aR1 signaling in osteoblasts might possibly affect RANKL/OPG balance, leading to increased bone resorption. Additional trauma significantly impaired fracture healing, particularly in Col1a1-C5aR1 mice. In conclusion, the data indicate that C5aR1 signaling in osteoblasts plays a detrimental role in bone regeneration after fracture.
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Registered trials
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