Sox-4 Messenger RNA Is Expressed in the Embryonic Growth Plate and Regulated via the Parathyroid Hormone/Parathyroid Hormone-Related Protein Receptor in Osteoblast-like Cells

Reppe, Sjur; Rian, Edith; Jemtland, Rune; Olstad, Ole Kristoffer; Gautvik, Vigdis T.; Gautvik, Kaare M.

doi:10.1359/jbmr.2000.15.12.2402

Cited by 33 publications

(26 citation statements)

References 61 publications

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“…Acute Sox4 knockdown (>50% by siRNA) in normal calvarial osteoblasts in vitro reduced the mRNA levels for PTHR1 and PTHrP, which is interesting also in light of our previous observation that Sox4 is a PTH-responsive gene (Reppe et al, 2000). Thus, Sox4 is not only a target for PTHR1 signaling, but may also be part of a regulatory loop that modulates the PTH/PTHrP-receptor system (Kronenberg, 2006).…”

Section: The Differences Between Sox4mentioning

confidence: 54%

“…Our group first reported expression of Sox4 in skeletal tissue; Sox4 mRNA is highly expressed in normal and clonal osteoblasts of human and rat origin, where it is stimulated by parathyroid hormone (PTH), and the transcript is predominantly localized in hypertrophic chondrocytes in developing mouse hindlimbs (Reppe et al, 2000). We recently demonstrated elevated SOX4 mRNA levels in bone biopsies from patients with active primary hyperparathyroidism compared with levels after successful surgery and PTH normalization (Reppe et al, 2006).…”

Section: Microcomputed Tomography (Ct) Histomorphometry and Biomechamentioning

confidence: 99%

“…We have previously shown that Sox4 mRNA is highly expressed in hypertrophic chondrocytes of the mouse embryonic growth plate during early phases (ED15.5) of endochondral bone development, and also by human and rodent osteoblasts in vitro (Reppe et al, 2000). Whereas cRNA in situ hybridization was not sufficiently sensitive to detect Sox4 mRNA in osteoblasts in vivo, real-time PCR enabled us to verify reduced Sox4 expression in bones from Sox4 +/-mice relative to WT (in vivo), as well as in the respective calvarial osteoblast cultures derived from these animals (in vitro).…”

Section: The Differences Between Sox4mentioning

confidence: 99%

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Osteopenia, decreased bone formation and impaired osteoblast development inSox4heterozygous mice

Nissen‐Meyer

Jemtland

Gautvik

et al. 2007

Journal of Cell Science

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The transcription factor Sox4 is vital for fetal development, as Sox4–/– homozygotes die in utero. Sox4 mRNA is expressed in the early embryonic growth plate and is regulated by parathyroid hormone, but its function in bone modeling/remodeling is unknown. We report that Sox4+/– mice exhibit significantly lower bone mass (by dual-energy X-ray absorptiometry) from an early age, and fail to obtain the peak bone mass of wild-type (WT) animals. Microcomputed tomography (μCT), histomorphometry and biomechanical testing of Sox4+/– bones show reduced trabecular and cortical thickness, growth plate width, ultimate force and stiffness compared with WT. Bone formation rate (BFR) in 3-month-old Sox4+/– mice is 64% lower than in WT. Primary calvarial osteoblasts from Sox4+/– mice demonstrate markedly inhibited proliferation, differentiation and mineralization. In these cultures, osterix (Osx) and osteocalcin (OCN) mRNA expression was reduced, whereas Runx2 mRNA was unaffected. No functional defects were found in osteoclasts. Silencing of Sox4 by siRNA in WT osteoblasts replicated the defects observed in Sox4+/– cells. We demonstrate inhibited formation and altered microarchitecture of bone in Sox4+/– mice versus WT, without apparent defects in bone resorption. Our results implicate the transcription factor Sox4 in regulation of bone formation, by acting upstream of Osx and independent of Runx2.

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Section: The Differences Between Sox4mentioning

confidence: 54%

Section: Microcomputed Tomography (Ct) Histomorphometry and Biomechamentioning

confidence: 99%

Section: The Differences Between Sox4mentioning

confidence: 99%

See 1 more Smart Citation

Osteopenia, decreased bone formation and impaired osteoblast development inSox4heterozygous mice

Nissen‐Meyer

Jemtland

Gautvik

et al. 2007

Journal of Cell Science

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“…Surprisingly, the SOX4 gene (40), which has received little attention, was expressed much earlier than the SOX5, SOX6, and SOX9 genes, which have been extensively studied (16).…”

Section: Discussionmentioning

confidence: 99%

In vitrocartilage formation by human adult stem cells from bone marrow stroma defines the sequence of cellular and molecular events during chondrogenesis

Sekiya

Vuoristo

Larson

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

605

502

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One approach to resolving the complexities of chondrogenesis is to examine simplified systems in vitro. We analyzed cartilage differentiation by human adult stem cells from bone marrow stroma. Marrow stromal cells were cultured as micromass pellets for 21 days in serum-free medium containing transforming growth factor (TGF)-␤3, dexamethasone, and bone morphogenetic protein (BMP)-6. Assays for pulse-labeled

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“…SOX2 is expressed in embryonic neural epithelial stem cells (46) and is essential to maintain pluripotent, self-renewal, and undifferentiated phenotypes of embryonic stem cells (47). SOX4 and SOX11 play a role in central nervous system development (48), and SOX4 gene recently was characterized as a component of the parathyroid hormone signal transduction pathway in osteoblastic cells and has an important function in bone formation (49). The chemokine receptor CXCR4 has been regarded as a MSC and NSC receptor that mediates MSC-specific migration to bone marrow and NSC migration to injury sites in the central nervous system (50,51).…”

Section: Primary Glioblastoma Biopsies Express Mesenchymal and Nsc-asmentioning

confidence: 99%

Primary Glioblastomas Express Mesenchymal Stem-Like Properties

Tso

Shintaku

Chen³

et al. 2006

Molecular Cancer Research

211

214

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Glioblastoma is the most common and aggressive primary brain cancer. Recent isolation and characterization of brain tumor-initiating cells supports the concept that transformed neural stem cells may seed glioblastoma. We previously identified a wide array of mesenchymal tissue transcripts overexpressed in a broad set of primary glioblastoma (de novo) tumors but not in secondary glioblastoma (derived from lower-grade) tumors, low-grade astrocytomas, or normal brain tissues. Here, we extend this observation and show that a subset of primary glioblastoma tumors and their derived tumor lines express cellular and molecular markers that are associated with mesenchymal stem cells (MSC) and that glioblastoma cell cultures can be induced to differentiate into multiple mesenchymal lineage-like cell types. These findings suggest either that a subset of primary glioblastomas derive from transformed stem cells containing MSC-like properties and retain partial phenotypic aspects of a MSC nature in tumors or that glioblastomas activate a series of genes that result in mesenchymal properties of the cancer cells to effect sustained tumor growth and malignant progression. (Mol Cancer Res 2006;4(9):607 -19)

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Sox-4 Messenger RNA Is Expressed in the Embryonic Growth Plate and Regulated via the Parathyroid Hormone/Parathyroid Hormone-Related Protein Receptor in Osteoblast-like Cells

Abstract: ABSTRACT

Cited by 33 publications

References 61 publications

Osteopenia, decreased bone formation and impaired osteoblast development inSox4heterozygous mice

Osteopenia, decreased bone formation and impaired osteoblast development inSox4heterozygous mice

In vitrocartilage formation by human adult stem cells from bone marrow stroma defines the sequence of cellular and molecular events during chondrogenesis

Primary Glioblastomas Express Mesenchymal Stem-Like Properties

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