Transforming growth factor-β1-induced N-cadherin drives cell–cell communication through connexin43 in osteoblast lineage

Yang, Yueyi; Liu, Wenjing; Wei, Jieya; Cui, Yujia; Zhang, Demao; Xie, Jing

doi:10.1038/s41368-021-00119-3

Cited by 21 publications

(11 citation statements)

References 44 publications

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“…Furthermore, we investigated if other cartilage-protective factors could prevent Cx43 reduction by TNFα. Anabolic factors, such as IGF, HGF, PDGF and TGF, have been shown to increase Cx43 expression in different tissues and cell types [ 29 , 30 , 31 , 32 , 33 ]. Among them, TGF-β1 action has been previously described in CH [ 12 ].…”

Section: Resultsmentioning

confidence: 99%

Dynamics of Connexin 43 Down Modulation in Human Articular Chondrocytes Stimulated by Tumor Necrosis Factor Alpha

Morte

Niada

Giannasi

et al. 2022

IJMS

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Connexin 43 (Cx43) exerts pivotal functions in articular chondrocytes (CH). It is involved in the communication among cells and between cells and the extracellular environment, and it contributes to the maintenance of the correct cell phenotype. The pro-inflammatory cytokine TNFα induces a reduction in Cx43 expression in CH. Here, we studied the dynamics of this decrease in expression. We evaluated Cx43 protein and gene expression and the involvement of C-terminal domain (CTD) cleavage and proteasomal degradation. Treatments able to counteract TNFα action were also examined, together with Gap Junction (GJ) functionality and Cx43 localization. TNFα induced a significant reduction in Cx43 expression already at day 1, and the down modulation reached a peak at day 3 (−46%). The decrease was linked to neither gene expression modulation nor CTD cleavage. Differently, the proteasome inhibitor MG132 reverted TNFα effect, indicating the involvement of proteasomal degradation in Cx43 reduction. In addition, the co-treatment with the anabolic factor TGF-β1 restored Cx43 levels. Cx43 decrease occurred both at the membrane level, where it partially influenced GJ communication, and in the nucleus. In conclusion, TNFα induced a rapid and lasting reduction in Cx43 expression mostly via the proteasome. The down modulation could be reverted by cartilage-protective factors such as MG132 and TGF-β1. These findings suggest a possible involvement of Cx43 perturbation during joint inflammation.

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Section: Resultsmentioning

confidence: 99%

Dynamics of Connexin 43 Down Modulation in Human Articular Chondrocytes Stimulated by Tumor Necrosis Factor Alpha

Morte

Niada

Giannasi

et al. 2022

IJMS

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“…WCHSIRB-OT-2020-048). The cells used in the experiments were all isolated from C57BL/6J mice (1–3 days old) as previously described [ 65 , 66 ]. Immature chondrocytes isolated from epiphyseal hyaline cartilage were extracted from knee joints.…”

Section: Methodsmentioning

confidence: 99%

SDF-1α Promotes Chondrocyte Autophagy through CXCR4/mTOR Signaling Axis

Chen

Cai

et al. 2023

IJMS

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SDF-1α, the most common isoform of stromal cell-derived factor 1, has shown vital effects in regulating chondrocyte proliferation, maturation, and chondrogenesis. Autophagy is a highly conserved biological process to help chondrocytes survive in harsh environments. However, the effect of SDF-1α on chondrocyte autophagy is still unknown. This study aims to investigate the effect of SDF-1α on chondrocyte autophagy and the underlying biomechanism. Transmission electron microscope assays and mRFP-GFP-LC3 adenovirus double label transfection assays were performed to detect the autophagic flux of chondrocytes. Western blots and immunofluorescence staining assays were used to detect the expression of autophagy-related proteins in chondrocytes. RNA sequencing and qPCR were conducted to assess changes in autophagy-related mRNA expression. SDF-1α upregulated the number of autophagosomes and autolysosomes in chondrocytes. It also increased the expression of autophagy-related proteins including ULK-1, Beclin-1 and LC3B, and decreased the expression of p62, an autophagy substrate protein. SDF-1α-mediated autophagy of chondrocytes required the participation of receptor CXCR4. Moreover, SDF-1α-enhanced autophagy of chondrocytes was through the inhibition of phosphorylation of mTOR signaling on the upstream of autophagy. Knockdown by siRNA and inhibition by signaling inhibitor further confirmed the importance of the CXCR4/mTOR signaling axis in SDF-1α-induced autophagy of chondrocytes. For the first time, this study elucidated that SDF-1α promotes chondrocyte autophagy through the CXCR4/mTOR signaling axis.

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“…CDM scaffolds were novel culture systems for comparing the chondrogenesis of different stem cells under different culture conditions. 182 3D-Printed chitosan scaffold TGF-β3 and BMP6 Human infrapatellar fat pad adipose stem cells (IPFP-ASCs) 1. A cartilage-like matrix formed the top layer of a 3D-printed chitosan scaffold 2.…”

Section: Potential Therapeutic Roles Of Tgf-β3 In Osteoarthritis (Oa)mentioning

confidence: 99%

“…Several studies found synergy in the chondrogenic differentiation of ADSCs, bone marrow-derived mesenchymal stem cells (BMSCs), and periodontal ligament stem cells. 182 – 187 In addition, Yoo et al put forward an innovative idea, suggesting that a combination of TGF‑β3 and BMP6, which shows a synergistic effect on chondrogenesis, loaded into an efficient carrier such as exosomes, which themselves show a chondroprotective function, offers an effective approach to treat damaged cartilage in OA. 13 In addition to growth factors, agents such as heparin and HA enhance chondrogenesis when used in combination with TGF-β3.…”

Section: Potential Therapeutic Roles Of Tgf-β3 In Osteoarthritis (Oa)mentioning

confidence: 99%

The role of TGF-beta3 in cartilage development and osteoarthritis

Cai

Xie

2023

Bone Res

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Articular cartilage serves as a low-friction, load-bearing tissue without the support with blood vessels, lymphatics and nerves, making its repair a big challenge. Transforming growth factor-beta 3 (TGF-β3), a vital member of the highly conserved TGF-β superfamily, plays a versatile role in cartilage physiology and pathology. TGF-β3 influences the whole life cycle of chondrocytes and mediates a series of cellular responses, including cell survival, proliferation, migration, and differentiation. Since TGF-β3 is involved in maintaining the balance between chondrogenic differentiation and chondrocyte hypertrophy, its regulatory role is especially important to cartilage development. Increased TGF-β3 plays a dual role: in healthy tissues, it can facilitate chondrocyte viability, but in osteoarthritic chondrocytes, it can accelerate the progression of disease. Recently, TGF-β3 has been recognized as a potential therapeutic target for osteoarthritis (OA) owing to its protective effect, which it confers by enhancing the recruitment of autologous mesenchymal stem cells (MSCs) to damaged cartilage. However, the biological mechanism of TGF-β3 action in cartilage development and OA is not well understood. In this review, we systematically summarize recent progress in the research on TGF-β3 in cartilage physiology and pathology, providing up-to-date strategies for cartilage repair and preventive treatment.

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Transforming growth factor-β1-induced N-cadherin drives cell–cell communication through connexin43 in osteoblast lineage

Cited by 21 publications

References 44 publications

Dynamics of Connexin 43 Down Modulation in Human Articular Chondrocytes Stimulated by Tumor Necrosis Factor Alpha

Dynamics of Connexin 43 Down Modulation in Human Articular Chondrocytes Stimulated by Tumor Necrosis Factor Alpha

SDF-1α Promotes Chondrocyte Autophagy through CXCR4/mTOR Signaling Axis

The role of TGF-beta3 in cartilage development and osteoarthritis

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