Involvement of PI3K/Akt pathway in rat condylar chondrocytes regulated by PTHrP treatment

Deng, Zhennan; Liu, Yang; Wang, Chaopeng; Fan, Hongyi; Ma, Jianfeng; Yu, Haiyang

doi:10.1016/j.archoralbio.2014.04.012

Cited by 12 publications

(10 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These data are the first to demonstrate the participation of PI3Kγ in palatal bone remodeling. In line with our findings, rat condyles cultivated ex vivo and the length of condylar cartilage were increased after treatment with a PI3K inhibitor (Deng et al, 2014). However, in an organ culture system of embryonic mouse tibiae also treated with a PI3K inhibitor, significant growth reduction of the proliferating and particularly of the hypertrophic zone was detected (Ulici et al, 2008).…”

Section: Discussionsupporting

confidence: 91%

“…The PI3K/Akt pathway is a key regulator in the wide system of extracellular signaling pathways that control bone biology through the bone cells (Cui et al, 2020; Li et al, 2020) and in periodontal ligament cells (Shim et al, 2022; Xu et al, 2017). The expression of the p‐Akt protein in the maxillary bones was determined by Western Blot, and the absence of the PI3Kγ enzyme decreased the expression of the p‐Akt protein, in agreement with previous literature findings (Cui et al, 2020; Deng et al, 2014; Wang et al, 2020). Furthermore, PI3K signaling has been reported to be relevant for the development and maintenance of skeleton homeostasis (Fantauzzo & Soriano, 2014; Wang et al, 2020).…”

Section: Discussionsupporting

confidence: 91%

See 1 more Smart Citation

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

Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 91%

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

show abstract

“…The PI3K/Akt signalling pathway was an important regulator of cellular proliferation and differentiation in chondrocytes. 21,22 We found that CTGF could activate the protein level of p-Akt in a dosedependent manner (Figure 3A&B). At 50 ng/mL, CTGF increased the expressions of p-Akt in a time-dependent manner ( Figure 3C&D).…”

Section: Ctgf Triggers Pi3k/akt Signalling To Mediate the Expressiomentioning

confidence: 87%

CTGF facilitates cell‐cell communication in chondrocytes via PI3K/Akt signalling pathway

Zhou

Yuan

et al. 2021

Cell Proliferation

View full text Add to dashboard Cite

The articular cartilage is located on the surface of the connected bones, which promotes the joint to achieve three-dimensional movement with low-friction. This tissue contains extracellular matrix (ECM), mainly composed of type II collagen and proteoglycans. Chondrocytes are highly specialized cells embedded in the ECM, which are essential for locomotion and postnatal growth. Chondrocytes account for less than 10% of the total volume of articular cartilage, but are responsible for cartilaginous matrix maintenance, formation and repair throughout adulthood. 1 Proper cell-to-cell communication is essential for tissues to respond appropriately to physical or

show abstract

“…As shown in Figures 3 and 4, our results indicated that PTHrP regulated the expression of cell cycle (cyclin D1 and E2F1) genes, which might be related to the G1/S transition in preimplantation embryos. Furthermore, PTHrP increased the levels of cyclin D1 and p‐AKT through the PI3K/AKT pathway, which regulates cell proliferation and differentiation (Calvo et al, 2014; Deng et al, 2014; Guo et al, 2013). Our results in this study indicated that Pthrp depletion resulted in a decrease in AKT (Thr308) phosphorylation in cleavage‐stage embryos (Figure 5), suggesting that Pthrp depletion can inhibit the PI3K/AKT pathway, which may involve the regulation of cyclin D1 expression during preimplantation embryonic development.…”

Section: Discussionmentioning

confidence: 99%

“…PTHrP is extensively expressed in many fetal and adult tissues, and it plays biological roles in a variety of processes, including growth, differentiation, development, migration, and apoptosis in cells and organs (Moniz et al, 1990; Strewler, 2000). Several studies have reported that PTHrP induces the expression of cyclin D1 and phospho (p)‐AKT through the PI3K/AKT pathway, which regulates cell proliferation and differentiation (Calvo et al, 2014; Deng et al, 2014; Guo et al, 2013). PTHrP also represses chondrocyte hypertrophy by inducing the dephosphorylation and subsequent nuclear translocation of HDAC4 (Kozhemyakina et al, 2009; Nishimori et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

PTHrP promotes development of mouse preimplantation embryos through the AKT/cyclin D1 pathway and nuclear translocation of HDAC4

Guo

et al. 2021

Journal Cellular Physiology

View full text Add to dashboard Cite

Parathyroid hormone‐related protein (PTHrP), the main cause of humoral hypercalcemia in malignancies, promotes cell proliferation and delays terminal cell maturation during embryonic development. Our previous study reported that PTHrP plays important roles in blastocyst formation, pluripotency gene expression, and histone acetylation during mouse preimplantation embryonic development. In this study, we further investigated the mechanism of preimplantation embryonic development regulated by PTHrP. Our results showed that Pthrp depletion decreased both the developmental rate of embryos at the cleavage stage and the cell number of morula‐stage embryos. Pthrp‐depleted embryos had significantly decreased levels of cyclin D1, phospho (p)‐AKT (Thr308) and E2F1. However, Pthrp depletion did not cause significant changes in CDK4, β‐catenin or RUNX2 expression. In addition, our results indicated that Pthrp depletion promoted HDAC4 translocation from the cytoplasm to the nucleus in cleavage‐stage embryos by stimulating the activity of protein phosphatase 2A (PP2A), which resulted in dephosphorylation of HDAC4. Taken together, these results suggest that PTHrP regulates cleavage division progression and blastocyst formation through the AKT/cyclin D1 pathway and that PTHrP modulates histone acetylation patterns through nuclear translocation of HDAC4 via PP2A‐dependent HDAC4 dephosphorylation during preimplantation embryonic development in mice.

show abstract

Involvement of PI3K/Akt pathway in rat condylar chondrocytes regulated by PTHrP treatment

Cited by 12 publications

References 44 publications

Targeting phosphatidylinositol‐3‐kinase for inhibiting maxillary bone resorption

Targeting phosphatidylinositol‐3‐kinase for inhibiting maxillary bone resorption

CTGF facilitates cell‐cell communication in chondrocytes via PI3K/Akt signalling pathway

PTHrP promotes development of mouse preimplantation embryos through the AKT/cyclin D1 pathway and nuclear translocation of HDAC4

Contact Info

Product

Resources

About