ArticlePloS one2015
Thermally induced osteocyte damage initiates a remodelling signaling cascade.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- Osteolysis after cervical disc arthroplasty.European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society · 2020Pooled it
- Systemic and local effects of vancomycin-combined thermal exposure on Staphylococcus aureus infected rat femurs: a comparative study of hyperthermia and thermal ablation.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Effects of Thermal Environment on Bone Microenvironment: A Narrative Review.International journal of molecular sciences · 2025Review
- Article
- Multiscale morphological analysis of bone microarchitecture around Mg-10Gd implants.Bioactive materials · 2023Article
- How Magnetic Composites are Effective Anticancer Therapeutics? A Comprehensive Review of the Literature.International journal of nanomedicine · 2023Review
- Comparison of Surgical Smoke Generated During Electrosurgery with Aerosolized Particulates from Ultrasonic and High-Speed Cutting.Annals of biomedical engineering · 2021Article
- Osteocyte Apoptosis Contributes to Cold Exposure-induced Bone Loss.Frontiers in bioengineering and biotechnology · 2021Article
- Osteocyte TGFβ1‑Smad2/3 is positively associated with bone turnover parameters in subchondral bone of advanced osteoarthritis.International journal of molecular medicine · 2020Article
- The Effect of TBB, as an Initiator, on the Biological Compatibility of PMMA/MMA Bone Cement.International journal of molecular sciences · 2020Article
- Apoptotic Osteocytes Induce RANKL Production in Bystanders via Purinergic Signaling and Activation of Pannexin Channels.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2020Article
- A Comparative Assessment of Implant Site Viability in Humans and Rats.Journal of dental research · 2018Article
- Thermally induced osteocyte damage initiates pro-osteoclastogenic gene expression in vivo.Journal of the Royal Society, Interface · 2016Article
- Pelleted Bone Marrow Derived Mesenchymal Stem Cells Are Better Protected from the Deleterious Effects of Arthroscopic Heat Shock.Frontiers in physiology · 2016Article
- Bone Homeostasis and Repair: Forced Into Shape.Current rheumatology reports · 2015Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Thermal elevations experienced by bone during orthopaedic procedures, such as cutting and drilling, exothermal reactions from bone cement, and thermal therapies such as tumor ablation, can result in thermal damage leading to death of native bone cells (osteocytes, osteoblasts, osteoclasts and mesenchymal stem cells). Osteocytes are believed to be the orchestrators of bone remodeling, which recruit nearby osteoclast and osteoblasts to control resorption and bone growth in response to mechanical stimuli and physical damage. However, whether heat-induced osteocyte damage can directly elicit bone remodelling has yet to be determined. This study establishes the link between osteocyte thermal damage and the remodeling cascade. We show that osteocytes directly exposed to thermal elevations (47°C for 1 minute) become significantly apoptotic and alter the expression of osteogenic genes (Opg and Cox2). The Rankl/Opg ratio is consistently down-regulated, at days 1, 3 and 7 in MLO-Y4s heat-treated to 47°C for 1 minute. Additionally, the pro-osteoblastogenic signaling marker Cox2 is significantly up-regulated in heat-treated MLO-Y4s by day 7. Furthermore, secreted factors from heat-treated MLO-Y4s administered to MSCs using a novel co-culture system are shown to activate pre-osteoblastic MSCs to increase production of the pro-osteoblastic differentiation marker, alkaline phosphatase (day 7, 14), and calcium deposition (day 21). Most interestingly, an initial pro-osteoclastogenic signaling response (increase Rankl and Rankl/Opg ratio at day 1) followed by later stage pro-osteoblastogenic signaling (down-regulation in Rankl and the Rankl/Opg ratio and an up-regulation in Opg and Cox2 by day 7) was observed in non-heat-treated MLO-Y4s in co-culture when these were exposed to the biochemicals produced by heat-treated MLO-Y4s. Taken together, these results elucidate the vital role of osteocytes in detecting and responding to thermal damage by means of thermally induced apoptosis followed by a cascade of remodelling responses.
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