72 Erg and PTHRP Genetically Cooperate to Maintain Articular Cartilage Long-Term Function

Okabe, Takahiro; Ohta, Yoshiji; Asai, S.; Wakitani, Shigeyuki; Enomoto‐Iwamoto, Motomi; Pacifici, Maurizio; Iwamoto, Masahiro

doi:10.1016/s1063-4584(11)60099-x

Cited by 2 publications

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“…It is indicated that Erg may have an ability to make epiphyseal cartilage to form an articular cartilage‐like structure. Our recent study suggests that Erg directly stimulates PTHLH gene transcription through the conserved ets binding sites in the proximal promoter of PTHLH (Okabe et al, ). Because expression of PTHLH in articular cartilage requires Indian hedgehog (Ihh)‐derived signaling from diaphysis, Erg may enhance Ihh‐mediated PTHLH gene expression in articular chondrocytes, and its anti‐maturation activity could be partially mediated by PTHLH.…”

Section: Which Factors Control Articular Chondrocyte Phenotype?mentioning

confidence: 99%

Toward regeneration of articular cartilage

Iwamoto

Ohta

Larmour

et al. 2013

Birth Defects Research Pt C

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Articular cartilage is classified into permanent hyaline cartilage and has significant differences in structure, extracelluar matrix components, gene expression profile, and mechanical property from transient hyaline cartilage found in growth plate. In the process of synovial joint development, articular cartilage is originated from the interzone, developing at the edge of the cartilaginous anlagen, it establishes zonal structure over time and supports smooth movement of the synovial joint through life. The cascade actions of key regulators such as Wnts, GDF5, Erg, and PTHLH coordinate sequential steps of articular cartilage formation. Articular chondrocytes are restrictedly controlled not to differentiate into a hypertrophic stage by autocrine and paracrine factors and extracerllular matrix microenvironment, but retain potential to undergo hypertrophy. The basal calcified zone of articular cartilage is connected with subchondral bone, but not invaded by blood vessels nor replaced by bone, which is highly contrasted with the growth plate. Articular cartilage has limited regenerative capacity, but likely possesses and potentially uses intrinsic stem cell source in the superficial layer, Ranvier’s groove, the intra-articular tissues such as synovium and fat pad, and marrow below the subchondral bone. Considering the biological views on articular cartilage, several important points are raised for regeneration of articular cartilage. We should evaluate the nature of regenerated cartilage as permanent hyaline cartilage and not just hyaline cartilage. We should study how a hypertrophic phenotype of transplanted cells can be lastingly suppressed in regenerating tissue. Further, we should develop the methods and reagents to activate recruitment of intrinsic stem/progenitor cells into the damaged site.

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Section: Which Factors Control Articular Chondrocyte Phenotype?mentioning

confidence: 99%

Toward regeneration of articular cartilage

Iwamoto

Ohta

Larmour

et al. 2013

Birth Defects Research Pt C

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“…PTHrP was reported to maintain the continuous proliferation of chondrocytes and inhibit their terminal differentiation into hypertrophic chondrocytes after mitosis (Pelosi et al 2013;Singh et al 2018). One study has also shown that the partial regulatory effect of ERG on chondrocytes is mediated by PTHrP (Okabe et al 2011). This nding shows that ERG can regulate the differentiation and developmental direction of embryonic cartilage progenitor cells through PTHrP.…”

Section: Introductionmentioning

confidence: 99%

The miR-200b-3p/ERG/PTHrP Axis Mediates the Inhibitory Effect of Ethanol on the Differentiation of Rat Fetal Chondrocytes into Articular Cartilage

Chen

et al. 2021

Preprint

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Background This study aims to further explore cartilage development in prenatal ethanol exposure (PEE) offspring at different times to explore the specific time points and mechanism of ethanol-induced fetal cartilage dysplasia. Methods On gestational day (GD)14, GD17, and GD20, PEE fetal cartilage was evaluated by morphological analysis. RT-qPCR, immunohistochemistry, and immunofluorescence were used to detect the expression of cartilage marker genes and their regulatory factors. Bone marrow mesenchymal stem cells (BMSCs) were used to explore the effect of ethanol on the differentiation of chondrocytes. Additionally, we used inhibitors, overexpression plasmids and a luciferase reporter assay on GD17 chondrocytes to verify the mechanism. Findings: PEE significantly reduced cartilage matrix content and the expression of marker genes on GD17 and GD20 but had no effect on GD14. The inhibition of chondrogenic differentiation by PEE mainly occurred on GD14-17. Furthermore, the expression of miR-200b-3p was increased, while that of ERG and PTHrP was markedly reduced in PEE fetal cartilage. In vitro, ethanol (30–120 mM) inhibited the differentiation of BMSCs into chondrocytes in a concentration-dependent manner, accompanied by strong expression of miR-200b-3p and low expression of ERG and PTHrP. Moreover, PTHLH and ERG overexpressed, as well as a miR-200b-3p inhibitor reversed the inhibitory effect of ethanol on the differentiation of fetal chondrocytes. Furthermore, miR-200b-3p could target and negatively regulate ERG. Interpretation: PEE can significantly inhibit the development of articular cartilage, especially during articular cartilage formation. The mechanism is related to the decreased differentiation of fetal cartilage into articular cartilage mediated by the miR-200b-3p/ERG/PTHrP axis.

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72 Erg and PTHRP Genetically Cooperate to Maintain Articular Cartilage Long-Term Function

Cited by 2 publications

References 0 publications

Toward regeneration of articular cartilage

Toward regeneration of articular cartilage

The miR-200b-3p/ERG/PTHrP Axis Mediates the Inhibitory Effect of Ethanol on the Differentiation of Rat Fetal Chondrocytes into Articular Cartilage

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