ArticleBone2021
Interleukin-6 (IL-6) deficiency enhances intramembranous osteogenesis following stress fracture in mice.
Article in Bone, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
16 citing papers in PubMed, 28 citations in OpenAlex.
- Unraveling stress fractures: from cellular and molecular mechanisms to therapeutic approaches.Journal of orthopaedic translation · 2026Review
- Myokines in exercise‑mediated bone homeostasis: Molecular signaling mechanisms and therapeutic implications for bone disorders (Review).International journal of molecular medicine · 2026Review
- The Scientific Case for Animal Models: A Perspective From Musculoskeletal Researchers.FASEB bioAdvances · 2026Article
- The Inflammation-Energy Metabolism Axis: A Central Driver of Sarcopenia-Osteoporosis: A Narrative Review.Calcified tissue international · 2026Review
- Early effects of α7nAChR regulation on maxillary expansion in mice : A study on osteogenesis and inflammatory factors.Journal of orofacial orthopedics = Fortschritte der Kieferorthopadie : Organ/official journal Deutsche Gesellschaft fur Kieferorthopadie · 2026Article
- Article
- YAP regulates transcriptional programs for layer-specific periosteal expansion during fracture repair.Science advances · 2025Article
- HMGB1 as an emerging key modulator of bone remodeling: a narrative review.Stem cell research & therapy · 2025Review
- Associations of Markers of Inflammatory Status and Adiposity with Bone Phenotype at Age 60-64 Years: Findings from the MRC National Survey of Health and Development.Calcified tissue international · 2025Article
- Advances in the application and research of biomaterials in promoting bone repair and regeneration through immune modulation.Materials today. Bio · 2025Review
- Fracture-Induced Immunological Cascades Trigger Rapid Systemic Bone Loss via Osteocyte-Regulated Osteoclastogenesis.ImmunoTargets and therapy · 2025Article
- [Perioperative changes of serum interleukin 6 levels in elderly male patients with intertrochanteric fracture].Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery · 2024Article
- Exploring the Role of Hormones and Cytokines in Osteoporosis Development.Biomedicines · 2024Review
- Advances with Platelet-Rich Plasma for Bone Healing.Biologics : targets & therapy · 2024Review
- Temporal transcriptome highlights the involvement of cytokine/JAK/STAT3 signaling pathway in the osteoinduction of BMSCs.Journal of orthopaedic surgery and research · 2023Article
- Network proteomic analysis identifies inter-alpha-trypsin inhibitor heavy chain 4 during early human Achilles tendon healing as a prognostic biomarker of good long-term outcomes.Frontiers in immunology · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Interleukin-6 (IL-6) is highly upregulated in response to skeletal injury, suggesting it plays a role in the inflammatory phase of fracture repair. However, the impact of IL-6 on successful repair remains incompletely defined. Therefore, we investigated the role of IL-6 in two models of fracture repair (full fracture and stress fracture) using 12-week old IL-6 global knockout mice (IL-6 KO) and wild type (WT) littermate controls. Callus morphology and mineral density 14 days after full femur fracture did not differ between IL-6 knockout mice and controls. In contrast, IL-6 KO mice had an enhanced bone response 7 days after ulnar stress fracture compared to WT, with increased total callus volume (p = 0.020) and callus bone volume (p = 0.045). IL-6 KO did not alter the recruitment of immune cells (Gr-1 or F4/80 positive) to the stress fracture callus. IL-6 KO also did not alter the number of osteoclasts in the stress fracture callus. Using RNA-seq, we identified differentially expressed genes in stress fracture vs. contralateral control ulnae, and observed that IL-6 KO resulted in only modest alterations to the gene expression response to stress fracture (SFx). Wnt1 was more highly upregulated in IL-6 KO SFx callus at both day 1 (fold change 12.5 in KO vs. 5.7 in WT) and day 3 (fold change 4.7 in KO vs. 1.9 in WT). Finally, using tibial compression to induce bone formation without bone injury, we found that IL-6 KO directly impacted osteoblast function, increasing the propensity for woven bone formation. In summary, we report that IL-6 knockout enhanced formation of callus and bone following stress fracture injury, likely through direct action on the osteoblast's ability to produce woven bone. This suggests a novel role of IL-6 as a suppressor of intramembranous bone formation.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.