Stiffened fibre-like microenvironment based on patterned equidistant micropillars directs chondrocyte hypertrophy

Duan, Mengmeng; Xia, Shuang; Liu, Yang; Pu, Xiaohua; Chen, Yukun; Zhou, Yifei; Huang, Mengxing; Pi, Caixia; Zhang, Demao; Xie, Jing

doi:10.1016/j.mtbio.2023.100682

Cited by 8 publications

(5 citation statements)

References 86 publications

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“…The mechanical microenvironment is an important regulator of osteocyte behaviors, including proliferation, differentiation, and communication. − In the current study, to mimic the actual complex hierarchical structure composed of unidirectionally aligned matrix-fibrils in bone tissue, we generated a patterned equidistant micropillar cell platform using PDMS. To interpret the change in osteocyte behaviors triggered by microenvironmental stiffness, we seeded osteocytes on these stiff/soft patterned equidistant micropillar substrates.…”

Section: Discussionmentioning

confidence: 99%

Biomimetic Fibers Derived from an Equidistant Micropillar Platform Dictate Osteocyte Fate via Mechanoreception

Liu

Duan

et al. 2023

Nano Lett.

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It is a big challenge to design a biomimetic physical microenvironment with greater similarity to in vivo tissue to observe real cell behaviors. We established a novel cell culture platform based on patterned equidistant micropillars with stiff and soft stiffnesses to mimic the changes that happened in the transition from normal to osteoporotic disease. We first demonstrated that the soft micropillar substrate decreased osteocyte synaptogenesis through synaptogyrin 1 and that this decrease was accompanied by impairment of cell mechanoperception and a decrease in cellular cytoskeletal rearrangement. We then found that the soft equidistant micropillar substrate reduced the osteocyte synaptogenesis mainly via the inactivation of Erk/MAPK signaling. We finally found that soft micropillar substrate-mediated synaptogenesis impacted the cell-to-cell communication and matrix mineralization of osteocytes. Taken together, this study provides evidence of cellular mechanical responses that are much more similar to those of real osteocytes at the bone tissue level.

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Section: Discussionmentioning

confidence: 99%

Biomimetic Fibers Derived from an Equidistant Micropillar Platform Dictate Osteocyte Fate via Mechanoreception

Liu

Duan

et al. 2023

Nano Lett.

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“…LY294002 (A8205, APExBIO, 10 μM) and AG1296 (A2477, APExBIO, 10 μM) were used to incubate DPSCs, respectively, for 4 h prior to PDGF‐AA. Total protein, cytoplasmic proteins and membrane proteins were acquired and separated according to the protocols (Duan et al., 2023; Xu et al., 2022). Equal amounts of protein samples were separated by SDS‐polyacrylamide gel electrophoresis and then transferred to a PVDF membrane (IPVH00010, Millipore, USA) at 250 mA for 90 min.…”

Section: Methodsmentioning

confidence: 99%

PDGF‐AA guides cell crosstalk between human dental pulp stem cells in vitro via the PDGFR‐α/PI3K/Akt axis

Xu,

Wei,

Liu

et al. 2024

Int Endodontic J

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AimTo explore the influence of PDGF‐AA on cell communication between human dental pulp stem cells (DPSCs) by characterizing gap junction intercellular communication (GJIC) and its potential biomechanical mechanism.MethodologyQuantitative real‐time PCR was used to measure connexin family member expression in DPSCs. Cell migration and CCK‐8 assays were utilized to examine the influence of PDGF‐AA on DPSC migration and proliferation. A scrape loading/dye transfer assay was applied to evaluate GJIC triggered by PDGF‐AA, a PI3K/Akt signalling pathway blocker (LY294002) and a PDGFR‐α blocker (AG1296). Western blotting and immunofluorescence were used to test the expression and distribution of the Cx43 and p‐Akt proteins in DPSCs. Scanning electron microscopy (SEM) and immunofluorescence were used to observe the morphology of GJIC in DPSCs.ResultsPDGF‐AA promoted gap junction formation and intercellular communication between human dental pulp stem cells. PDGF‐AA upregulates the expression of Cx43 to enhance gap junction formation and intercellular communication. PDGF‐AA binds to PDGFR‐α and activates PI3K/Akt signalling to regulate cell communication.ConclusionsThis research demonstrated that PDGF‐AA can enhance Cx43‐mediated GJIC in DPSCs via the PDGFR‐α/PI3K/Akt axis, which provides new cues for dental pulp regeneration from the perspective of intercellular communication.

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“…Chondrocytes were treated with FGF19 and KLB at 50, 100, and 200 ng/ml for 72 h, respectively. BLU9931 (5 μM, 5387760001, Sigma, MO, USA) and SB203580 (10 μM, A8254, APExBIO, TX, USA) was added 2 h prior to FGF19 and KLB treatment as previously described [ 58 , 59 ]. RIPA lysis buffer (68117726, Biosharp, Hefei, China) was used to extract protein.…”

Section: Methodsmentioning

confidence: 99%

FGF19 induces the cell cycle arrest at G2-phase in chondrocytes

Chen

et al. 2023

Cell Death Discov.

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Fibroblast growth factor 19 (FGF19) has appeared as a new possible avenue in the treatment of skeletal metabolic disorders. However, the role of FGF19 on cell cycle progression in skeletal system is poorly understood. Here we demonstrated that FGF19 had the ability to reduce the proliferation of chondrocytes and cause cell cycle G2 phase arrest through its interaction with β-Klotho (KLB), an important accessory protein that helps FGF19 link to its receptor. FGF19-mediated cell cycle arrest by regulating the expressions of cdk1/cylinb1, chk1 and gadd45a. We then confirmed that the binding of FGF19 to the membrane receptor FGFR4 was necessary for FGF19-mediated cell cycle arrest, and further proved that FGF19-mediated cell cycle arrest was via activation of p38/MAPK signaling. Through inhibitor experiments, we discovered that inhibition of FGFR4 led to down-regulation of p38 signaling even in the presence of FGF19. Meanwhile, inhibiting p38 signaling reduced the cell cycle arrest of chondrocytes induced by FGF19. Furthermore, blocking p38 signaling facilitated to retain the expression of cdk1 and cyclinb1 that had been reduced in chondrocytes by FGF19 and decreased the expression of chk1 and gadd45a that had been enhanced by FGF19 in chondrocytes. Taking together, this study is the first to demonstrate that FGF19 induces cell cycle arrest at G2 phase via FGFR4-p38/MAPK axis and enlarges our understanding about the role of FGF19 on cell cycle progression in chondrocytes.

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Stiffened fibre-like microenvironment based on patterned equidistant micropillars directs chondrocyte hypertrophy

Cited by 8 publications

References 86 publications

Biomimetic Fibers Derived from an Equidistant Micropillar Platform Dictate Osteocyte Fate via Mechanoreception

Biomimetic Fibers Derived from an Equidistant Micropillar Platform Dictate Osteocyte Fate via Mechanoreception

PDGF‐AA guides cell crosstalk between human dental pulp stem cells in vitro via the PDGFR‐α/PI3K/Akt axis

FGF19 induces the cell cycle arrest at G2-phase in chondrocytes

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