Smad-Runx Interactions During Chondrocyte Maturation

Leboy, Phoebe S.; Grasso-Knight, Giovi; D’Angelo, Marina; Volk, Susan W.; Lian, Jane V.; Drissi, Hicham; Stein, Gary S.; Adams, Sherrill L.

doi:10.2106/00004623-200100001-00003

Cited by 109 publications

(109 citation statements)

References 47 publications

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“…Co-regulation by miR-455 and Runx2 has been indirectly found in several studies. It has been shown that Runx-2 could co-regulate chondrogenesis with Smad genes [36,37], and miR-455 can suppress the Smad pathway during chondrogenesis [5]. We further tested the co-regulation of miR-455-3p and Runx2 by the transfection of a miR-455-3p mimic or inhibitor; the result showed that the miR-455-3p mimic or inhibitor inhibited or induced Runx2 expression, respectively.…”

Section: Discussionmentioning

confidence: 99%

MiR‐455‐3p regulates early chondrogenic differentiation via inhibiting Runx2

et al. 2015

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Edited by Zhijie ChangKeywords: Chondrogenesis MiR-455-3p Runt-related transcription factor 2 a b s t r a c tThe expression of miR-455-3p has been shown to be up-regulated in chondrogenesis of mesenchymal stem cell, but its role in different stages during chondrogenesis remains unknown. Here, we show that miR-455-3p is increased in ATDC5 cells from 0 d to 21 d, but rapidly decreases at 28 d, and a similar expression kinetic is detected in the development of mouse embryos. We show that miR-455-3p functions as an activator for early chondrogenic differentiation, most likely by inhibiting the expression of Runt-related transcription factor 2 (Runx2) as indicated by luciferase reporter assays. In conclusion, miR-455-3p may activate early chondrogenesis by directly targeting Runx2.

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Section: Discussionmentioning

confidence: 99%

MiR‐455‐3p regulates early chondrogenic differentiation via inhibiting Runx2

et al. 2015

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“…BMPs maintain expression of Sox9 and subsequent cartilage matrix production (10,11). BMPs are also required in vitro for the induction of Col2a1 and Col10a1 to promote chondrocyte maturation at later stages (12)(13)(14). Chondrocyte-specific overexpression of the extracellular BMP antagonist, Noggin, in transgenic mice resulted in no cartilage formation (15).…”

Section: Although Bone Morphogenic Protein (Bmp) Signaling Promotes Cmentioning

confidence: 99%

“…Similarly, mice with cartilage-specific combined deletions of two BMP type I receptor genes (Bmpr1a and Bmpr1b), or with a double knock-out of Smad1 and Smad5, showed severely impaired chondrogenesis (16,17). At a later maturation stage, BMP signaling directly accelerates the expression of Col10a1 in concert with Runx2 (13,18,19). Forced expression of constitutively active Bmpr1a in cartilage promoted the maturation and hypertrophy of chondrocytes in mice (20).…”

Section: Although Bone Morphogenic Protein (Bmp) Signaling Promotes Cmentioning

confidence: 99%

Bone Morphogenic Protein (BMP) Signaling Up-regulates Neutral Sphingomyelinase 2 to Suppress Chondrocyte Maturation via the Akt Protein Signaling Pathway as a Negative Feedback Mechanism

Kakoi

Maeda

Shinohara

et al. 2014

Journal of Biological Chemistry

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Background: It is not clear how BMP-induced chondrocyte maturation is cell-autonomously terminated. Results: BMP-2 induced the ceramide-generating enzyme neutral sphingomyelinase 2 (nSMase2) in chondrocytes, whereas silencing of nSMase2 enhanced maturation in an Akt signaling-dependent manner. Conclusion: nSMase2 signaling regulates BMP-induced chondrocyte maturation as a negative feedback mechanism. Significance: This study elucidated the novel link between BMP and lipid signaling in chondrogenesis.

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“…Mad, a Drosophila homologue of Smad, was shown to directly bind to the enhancer of these genes and GCCGnCGC (GCCG motif) was identified as the consensus binding site. It has been reported that Smads 1 and 5 interact with bone-specific transcription factor Runx2 (Hanai et al, 1999;Lee et al, 2000;Zhao et al, 2003) and activate the transcription of target genes such as COX-2 and type X collagen (Col-X) in osteoblasts or in chondrocytes (Chikazu et al, 2002;Leboy et al, 2001). The association of Smad1 with homeodomain-containing proteins suggests another important mechanism of BMP signaling in osteoblasts and in chondrocytes.…”

Section: Bmp Signal Transductionmentioning

confidence: 99%

The BMP signaling and in vivo bone formation

Cao

Chen

2005

Gene

272

197

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Bone morphogenetic proteins (BMPs) are multi-functional growth factors that belong to the transforming growth factor β(TGFβ) superfamily. The roles of BMPs in embryonic development and cellular functions in postnatal and adult animals have been extensively studied in recent years. Signal transduction studies have revealed that Smads 1, 5 and 8 are the immediate downstream molecules of BMP receptors and play a central role in BMP signal transduction. Studies from transgenic and knockout mice and from animals and humans with naturally occurring mutations in BMPs and their signaling molecules have shown that BMP signaling plays critical roles in bone and cartilage development and postnatal bone formation. BMP activities are regulated at different molecular levels. Tissue-specific knockout of a specific BMP ligand, a subtype of BMP receptors or a specific signaling molecule is required to further determine the specific role of a BMP ligand, receptor or signaling molecule in a particular tissue.

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Smad-Runx Interactions During Chondrocyte Maturation

Cited by 109 publications

References 47 publications

MiR‐455‐3p regulates early chondrogenic differentiation via inhibiting Runx2

MiR‐455‐3p regulates early chondrogenic differentiation via inhibiting Runx2

Bone Morphogenic Protein (BMP) Signaling Up-regulates Neutral Sphingomyelinase 2 to Suppress Chondrocyte Maturation via the Akt Protein Signaling Pathway as a Negative Feedback Mechanism

The BMP signaling and in vivo bone formation

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