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  • Wang, Xijun  (2)
  • Medicine  (2)
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  • Medicine  (2)
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  • 1
    In: Journal of Bone and Mineral Research, Wiley, Vol. 38, No. 1 ( 2023-01), p. 214-227
    Abstract: Mechanical force is essential to shape the internal architecture and external form of the skeleton by regulating the bone remodeling process. However, the underlying mechanism of how the bone responds to mechanical force remains elusive. Here, we generated both orthodontic tooth movement (OTM) model in vivo and a cyclic stretch‐loading model in vitro to investigate biomechanical regulation of the alveolar bone. In this study, signal transducer and activator of transcription 3 (STAT3) was screened as one of the mechanosensitive proteins by protein array analysis of cyclic stretch‐loaded bone mesenchymal stem cells (BMSCs) and was also proven to be activated in osteoblasts in response to the mechanical force during OTM. With an inducible osteoblast linage‐specific Stat3 knockout model, we found that Stat3 deletion decelerated the OTM rate and reduced orthodontic force‐induced bone remodeling, as indicated by both decreased bone resorption and formation. Both genetic deletion and pharmacological inhibition of STAT3 in BMSCs directly inhibited mechanical force‐induced osteoblast differentiation and impaired osteoclast formation via osteoblast–osteoclast cross‐talk under mechanical force loading. According to RNA‐seq analysis of Stat3 ‐deleted BMSCs under mechanical force, matrix metalloproteinase 3 ( Mmp3) was screened and predicted to be a downstream target of STAT3 . The luciferase and ChIP assays identified that Stat3 could bind to the Mmp3 promotor and upregulate its transcription activity. Furthermore, STAT3‐inhibitor decelerated tooth movement through inhibition of the bone resorption activity, as well as MMP3 expression. In summary, our study identified the mechanosensitive characteristics of STAT3 in osteoblasts and highlighted its critical role in force‐induced bone remodeling during orthodontic tooth movement via osteoblast–osteoclast cross‐talk. © 2022 American Society for Bone and Mineral Research (ASBMR).
    Type of Medium: Online Resource
    ISSN: 0884-0431 , 1523-4681
    URL: Issue
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2008867-X
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  • 2
    In: Journal of Bone and Mineral Research, Oxford University Press (OUP), ( 2024-03-03)
    Abstract: Healthy alveolar bone is the cornerstone of oral function and oral treatment. Alveolar bone is highly dynamic during the entire lifespan and is affected by both systemic and local factors. Importantly, alveolar bone is subjected to unique occlusal force in daily life, and mechanical force is a powerful trigger of bone remodeling, but the effect of occlusal force in maintaining alveolar bone mass remains ambiguous. In this study, the Piezo1 channel is identified as an occlusal force sensor. Activation of Piezo1 rescues alveolar bone loss caused by a loss of occlusal force. Moreover, we identify Piezo1 as the mediator of occlusal force in osteoblasts, maintaining alveolar bone homeostasis by directly promoting osteogenesis and by sequentially regulating catabolic metabolism through Fas ligand (FasL)-induced osteoclastic apoptosis. Interestingly, Piezo1 activation also exhibits remarkable efficacy in the treatment of alveolar bone osteoporosis caused by estrogen deficiency, which is highly prevalent among middle-aged and elderly women. Promisingly, Piezo1 may serve not only as a treatment target for occlusal force loss-induced alveolar bone loss but also as a potential target for metabolic bone loss, especially in older patients.
    Type of Medium: Online Resource
    ISSN: 0884-0431 , 1523-4681
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2024
    detail.hit.zdb_id: 2008867-X
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
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