Osteoblastic STAT3 Is Crucial for Orthodontic Force Driving Alveolar Bone Remodeling and Tooth Movement

Gong, Xiangyang; Sun, S.; Yang, Yiling; Huang, Xiangru; Gao, Xin; Jin, Anting; Xu, Hongyuan; Wang, Xijun; Liu, Yuanqi; Liu, Jingyi; Dai, Qinggang; Jiang, Lingyong

doi:10.1002/jbmr.4744

Cited by 12 publications

(4 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…STAT3 deletion decreases bone mineral density 5 and slows orthodontic tooth movement by impeding osteoblast/osteoclast function in alveolar bone remodeling. 8 In this study, osteoblasts were force-loaded with the Flexcell Tension system to mimic the expansion force in vitro and screened for mechanosensitive characteristics of the STAT3 pathway. Upon mechanical stimulation, pJAK2 and pSTAT3 showed increased expression, as evidenced by western blotting.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Suppressing STAT3 activation impairs bone formation during maxillary expansion and relapse

et al. 2023

View full text Add to dashboard Cite

Objectives The mid-palatal expansion technique is commonly used to correct maxillary constriction in dental clinics. However, there is a tendency for it to relapse, and the key molecules responsible for modulating bone formation remain elusive. Thus, this study aimed to investigate whether signal transducer and activator of transcription 3 (STAT3) activation contributes to osteoblast-mediated bone formation during palatal expansion and relapse. Methodology In total, 30 male Wistar rats were randomly allocated into Ctrl (control), E (expansion only), and E+Stattic (expansion plus STAT3-inhibitor, Stattic) groups. Micro-computed tomography, micromorphology staining, and immunohistochemistry of the mid-palatal suture were performed on days 7 and 14. In vitro cyclic tensile stress (10% magnitude, 0.5 Hz frequency, and 24 h duration) was applied to rat primary osteoblasts and Stattic was administered for STAT3 inhibition. The role of STAT3 in mechanical loading-induced osteoblasts was confirmed by alkaline phosphatase (ALP), alizarin red staining, and western blots. Results The E group showed greater arch width than the E+Stattic group after expansion. The differences between the two groups remained significant after relapse. We found active bone formation in the E group with increased expression of ALP, COL-I, and Runx2, although the expression of osteogenesis-related factors was downregulated in the E+stattic group. After STAT3 inhibition, expansive force-induced bone resorption was attenuated, as TRAP staining demonstrated. Furthermore, the administration of Stattic in vitro partially suppressed tensile stress-enhanced osteogenic markers in osteoblasts. Conclusions STAT3 inactivation reduced osteoblast-mediated bone formation during palatal expansion and post-expansion relapse, thus it may be a potential therapeutic target to treat force-induced bone formation.

show abstract

Section: Discussionmentioning

confidence: 99%

“… 6 STAT3 is expressed in osteocytes and mediates force-induced bone formation in long bone 7 and orthodontic tooth movement. 8 Moreover, it is unclear so far whether STAT3 participates in RME-induced MPS and, if so, what exactly performs in bone formation.…”

Section: Introductionmentioning

confidence: 99%

Suppressing STAT3 activation impairs bone formation during maxillary expansion and relapse

et al. 2023

View full text Add to dashboard Cite

show abstract

“…The former is characterized by the abrupt development of areas of pressure and tension in the periodontal ligament. These force‐induced stresses alter the vascularization and blood flow of the periodontal ligament, leading to the local synthesis and release of several key molecules, such as growth factors, arachidonic acid metabolites, neurotransmitters, cytokines, colony‐stimulating factors, and biomarkers related to inflammation (Gong et al, 2023; Krishnan & Davidovitch, 2006; Pereira et al, 2020). Furthermore, these molecules can induce many cellular responses from different cell types in alveolar bone and teeth, creating a favorable microenvironment for tissue remodeling (Krishnan & Davidovitch, 2006).…”

Section: Discussionmentioning

confidence: 99%

Targeting phosphatidylinositol‐3‐kinase for inhibiting maxillary bone resorption

Santos,

Lima,

Barrioni

et al. 2023

Journal Cellular Physiology

View full text Add to dashboard Cite

Previous studies have suggested a role of phosphatidylinositol‐3‐kinase gamma (PI3Kγ) in bone remodeling, but the mechanism remains undefined. Here, we explored the contribution of PI3Kγ in the resorption of maxillary bone and dental roots using models of orthodontic tooth movement (OTM), orthodontic‐induced inflammatory root resorption, and rapid maxillary expansion (RME). PI3Kγ‐deficient mice (PI3Kγ−/−), mice with loss of PI3Kγ kinase activity (PI3KγKD/KD) and C57BL/6 mice treated with a PI3Kγ inhibitor (AS605240) and respective controls were used. The maxillary bones of PI3Kγ−/−, PI3KγKD/KD, and C57BL/6 mice treated with AS605240 showed an improvement of bone quality compared to their controls, resulting in reduction of the OTM and RME in all experimental groups. PI3Kγ−/− mice exhibited increased root volume and decreased odontoclasts counts. Consistently, the pharmacological blockade or genetic deletion of PI3K resulted in increased numbers of osteoblasts and reduction in osteoclasts during OTM. There was an augmented expression of Runt‐related transcription factor 2 (Runx2) and alkaline phosphatase (Alp), a reduction of interleukin‐6 (Il‐6), as well as a lack of responsiveness of receptor activator of nuclear factor kappa‐Β (Rank) in PI3Kγ−/− and PI3KγKD/KD mice compared to control mice. The maxillary bones of PI3Kγ−/− animals showed reduced p‐Akt expression. In vitro, bone marrow cells treated with AS605240 and cells from PI3Kγ−/− mice exhibited significant augment of osteoblast mineralization and less osteoclast differentiation. The PI3Kγ/Akt axis is pivotal for bone remodeling by providing negative and positive signals for the differentiation of osteoclasts and osteoblasts, respectively.

show abstract

“…[ 71 , 72 ] In osteoblastic deletion of Stat3 by Col1a1-CreER mice, OTM is inhibited due to the reduction in osteoblasts associated with a decrease in the number of osteoclasts on the compression side. [ 73 ] In experiments with a co-culture system of osteoblasts and osteoclasts under mechanical stimulation, Stat3 -deficient osteoblasts show a lower osteoclast induction ability. These results may suggest that mechanical stimulation by orthodontic treatment affects osteoclastogenesis by upregulating RANKL expression in osteoblasts via the IL-6-induced JAK2/STAT3 signaling pathway.…”

Section: Cytokines That Promote Osteoclastogenesis During Otmmentioning

confidence: 99%

Mechanisms of Osteoclastogenesis in Orthodontic Tooth Movement and Orthodontically Induced Tooth Root Resorption

Nakai,

Praneetpong,

Ono

et al. 2023

J Bone Metab

View full text Add to dashboard Cite

Orthodontic tooth movement (OTM) is achieved by the simultaneous activation of bone resorption by osteoclasts and bone formation by osteoblasts. When orthodontic forces are applied, osteoclast-mediated bone resorption occurs in the alveolar bone on the compression side, creating space for tooth movement. Therefore, controlling osteoclastogenesis is the fundamental tenet of orthodontic treatment. Orthodontic forces are sensed by osteoblast lineage cells such as periodontal ligament (PDL) cells and osteocytes. Of several cytokines produced by these cells, the most important cytokine promoting osteoclastogenesis is the receptor activator of nuclear factor-κB ligand (RANKL), which is mainly supplied by osteoblasts. Additionally, osteocytes embedded within the bone matrix, T lymphocytes in inflammatory conditions, and PDL cells produce RANKL. Besides RANKL, inflammatory cytokines, such as interleukin-1, tumor necrosis factor-α, and prostaglandin E2 promote osteoclastogenesis under OTM. On the downside, excessive osteoclastogenesis activation triggers orthodontically-induced external root resorption (ERR) through pro-osteoclastic inflammatory cytokines. Therefore, understanding the mechanisms of osteoclastogenesis during OTM is essential in reducing the adverse effects of orthodontic treatment. Here, we review the current concepts of the mechanisms underlying osteoclastogenesis in OTM and orthodontically induced ERR.

show abstract

Osteoblastic STAT3 Is Crucial for Orthodontic Force Driving Alveolar Bone Remodeling and Tooth Movement

Cited by 12 publications

References 46 publications

Suppressing STAT3 activation impairs bone formation during maxillary expansion and relapse

Suppressing STAT3 activation impairs bone formation during maxillary expansion and relapse

Targeting phosphatidylinositol‐3‐kinase for inhibiting maxillary bone resorption

Mechanisms of Osteoclastogenesis in Orthodontic Tooth Movement and Orthodontically Induced Tooth Root Resorption

Contact Info

Product

Resources

About