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

Wu, Zuping; Zhou, Chenchen; Yuan, Quan; Zhang, Demao; Xie, Jing; Zou, Shujuan

doi:10.1111/cpr.13001

Cited by 27 publications

(17 citation statements)

References 53 publications

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“…Intercellular communication mediated by Cx43 can promote the differentiation of ameloblasts and exhibits significant effects on enamel mineralization [ 38 ]. Our previous studies showed that Cx43 was a downstream target protein of CTGF in chondrocytes that regulated cell-to-cell communication [ 27 , 31 ]. Simultaneously, cementocytes specifically express Cx43 as a gap junction carrier to facilitate intercellular communication [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

“…The detailed immunofluorescence procedure was described previously [ 27 ]. The hPDLSCs were fixed in 4% PFA for 15 min.…”

Section: Methodsmentioning

confidence: 99%

“…The RNA interference protocol was consistent with a previous study [27]. hPDLSCs were seeded in 24-well, 48-well and 6-well culture dishes; transfected with the corresponding siRNA (Hanbio, China); and transiently transfected using Lipofectamine RNAiMAX (Invitrogen, Burlington, ON, Canada).…”

Section: Rna Interference For Cx43 and Ctgf Knockdownmentioning

confidence: 99%

“…A previous study by our team revealed that CTGF promoted cell‒cell communication and cell connection formation in chondrocytes in a Cx43-dependent manner, thus influencing cell biological processes, such as cell migration [ 27 ]. β-catenin acts as a signalling pathway downstream of Cx43 to regulate bone homeostasis [ 28 ].…”

Section: Introductionmentioning

confidence: 99%

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Connective tissue growth factor promotes cementogenesis and cementum repair via Cx43/β-catenin axis

Chen

et al. 2022

Stem Cell Res Ther

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Background Orthodontic tooth movement inevitably induces cementum resorption, which is an urgent problem for orthodontists to confront. Human periodontal ligament stem cells (hPDLSCs) exert an important role in the orthodontic tooth movement and exhibit multidirectional differentiation ability in cementum regeneration. Connective tissue growth factor (CTGF) is an important extracellular matrix protein for bone homeostasis and cell differentiation. The purpose of our study was to explore the role of CTGF in cementum repair and cementogenesis and to elucidate its underlying mechanism. Methods A cementum defect model was established by tooth movement with heavy forces, and the cementum repair effect of CTGF was observed via micro-CT, HE staining and immunohistochemical staining. RT‒qPCR, western blotting (WB), alizarin red staining and ALP activity experiments verified the mineralization ability of hPDLSCs stimulated with CTGF. The expression of Cx43 in periodontal ligament cells was detected by WB and immunofluorescence (IF) experiments after CTGF stimulation in vivo and in vitro. Subsequently, the mineralization ability of hPDLSCs was observed after application of CTGF and the small interfering RNA Si-Cx43. Additionally, co-intervention via application of the small interfering RNA Si-CTGF and the Cx43 agonist ATRA in hPDLSCs was performed to deepen the mechanistic study. Next, WB, IF experiments and co-immunoprecipitation were conducted to confirm whether CTGF triggers the Cx43/β-catenin axis to regulate cementoblast differentiation of hPDLSCs. Results Local oral administration of CTGF to the cementum defects in vivo facilitated cementum repair. CTGF facilitated the cementogenesis of hPDLSCs in a concentration-dependent manner. Cx43 acted as a downstream effector of CTGF to regulate cementoblast differentiation. Si-Cx43 reduced CTGF-induced cementoblast differentiation. The Cx43 agonist ATRA restored the low differentiation capacity induced by Si-CTGF. Further mechanistic studies showed that CTGF triggered the activation of β-catenin in a dose-dependent manner. In addition, co-localization IF analysis and co-immunoprecipitation demonstrated that Cx43 interacted with β-catenin at cell‒cell connections. Si-Cx43 attenuated the substantial expression of β-catenin induced by CTGF. The Cx43 agonist reversed the inhibition of β-catenin induced by Si-CTGF. IF demonstrated that the nuclear importation of β-catenin was related to the immense expression of Cx43 at cell‒cell junctions. Conclusions Taken together, these data demonstrate that CTGF promotes cementum repair and cementogenesis through activation of the Cx43/β-catenin signalling axis.

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Section: Discussionmentioning

confidence: 99%

“…The detailed immunofluorescence procedure was described previously [ 27 ]. The hPDLSCs were fixed in 4% PFA for 15 min.…”

Section: Methodsmentioning

confidence: 99%

Section: Rna Interference For Cx43 and Ctgf Knockdownmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Connective tissue growth factor promotes cementogenesis and cementum repair via Cx43/β-catenin axis

Chen

et al. 2022

Stem Cell Res Ther

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“…CTGF is also known as cellular communication network factor 2 (CCN2), which acts as a signal conductor for communication among chondrocytes by intercellular junctions between chondrocytes ( 49 ). Under rCTGF intervention, the migration efficiency of chondrocytes increased in a concentration-dependent manner, and the formation of intercellular junctions of chondrocytes were significantly increased.…”

Section: Under the Physiological Conditionmentioning

confidence: 99%

CTGF as a multifunctional molecule for cartilage and a potential drug for osteoarthritis

Yang

Song

et al. 2022

Front. Endocrinol.

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CTGF is a multifunctional protein and plays different roles in different cells and under different conditions. Pamrevlumab, a monoclonal antibody against CTGF, is an FDA approved drug for idiopathic pulmonary fibrosis (IPF) and Duchenne muscular dystrophy (DMD). Recent studies have shown that CTGF antibodies may potentially serve as a new drug for osteoarthritis (OA). Expression of CTGF is significantly higher in OA joints than in healthy counterparts. Increasing attention has been attracted due to its interesting roles in joint homeostasis. Joint homeostasis relies on normal cellular functions and cell-cell interactions. CTGF is essential for physiological activities of chondrocytes. Abnormal CTGF expression may cause cartilage degeneration. In this review, the physiological functions of CTGF in chondrocytes and related mechanisms are summarized. Changes in the related signaling pathways due to abnormal CTGF are discussed, which are contributing factors to inflammation, cartilage degeneration and synovial fibrosis in OA. The possibility of CTGF as a potential therapeutic target for OA treatment are reviewed.

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Outer Membrane Vesicles Derived From Fusobacterium nucleatum Trigger Periodontitis Through Host Overimmunity

Zhang,

Liu

et al. 2024

Advanced Science

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The virulent bacteria‐induced host immune response dominates the occurrence and progression of periodontal diseases because of the roles of individual virulence factors from these pathogens in the initiation and spread of inflammation. Outer membrane vesicles (OMVs) as a pathogenic entity have recently attracted great attention as messenger bridges between bacteria and host tissues. Herein, the novel role of OMVs derived from Fusobacterium nucleatum in the occurrence of periodontitis is dissected. In a rat periodontitis model, it is found that OMVs derived from F. nucleatum caused deterioration of periodontitis by enhancing inflammation of the periodontium and absorption of alveolar bone, which is almost equivalent to the effect of F. nucleatum itself. Furthermore, that OMVs can independently induce periodontitis is shown. The pathogenicity of OMVs is attributed to multiple pathogenic components identified by omics. After entering human periodontal ligament stem cells (hPDLSCs) by endocytosis, OMVs activated NLRP3 inflammasomes and impaired the mineralization of hPDLSCs through NF‐κB (p65) signaling, leading to the final injury of the periodontium and damage of alveolar bone in periodontitis. These results provide a new understanding of OMVs derived from pathogens and cues for the prevention of periodontitis.

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

Cited by 27 publications

References 53 publications

Connective tissue growth factor promotes cementogenesis and cementum repair via Cx43/β-catenin axis

Connective tissue growth factor promotes cementogenesis and cementum repair via Cx43/β-catenin axis

CTGF as a multifunctional molecule for cartilage and a potential drug for osteoarthritis

Outer Membrane Vesicles Derived From Fusobacterium nucleatum Trigger Periodontitis Through Host Overimmunity

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