Transcriptional regulation of the HOX4C gene by basic fibroblast growth factor on rheumatoid synovial fibroblasts

Xue, Chengsen; Hasunuma, Tomoko; Asahara, Hiroshi; Yin, Weihong; Maeda, Toshiro; Fujisawa, Kotaro; Dong, Yi; Sumida, Takayuki; Nishioka, Kusuki

doi:10.1002/art.1780400912

Cited by 9 publications

(12 citation statements)

References 42 publications

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“…We previously reported that HoxD9, one of the homeobox gene families which controls cell growth and pattern formation during embryogenesis, is overexpressed exclusively in rheumatoid synovium [23,24]. HoxD9 is a transcriptional factor that determines the planning of the body.…”

Section: Discussionmentioning

confidence: 99%

Expression of Notch homologues in the synovium of rheumatoid arthritis and osteoarthritis patients

Ishii

Nakazawa

Yoshino

et al. 2001

Rheumatology International

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Notch is known as a receptor that controls differentiation or proliferation in various cells and is associated with several diseases. The objective of the present study was to clarify whether human Notch homologues Notch-1, -2, -3, and -4 are expressed in synovium and synoviocytes from rheumatoid arthritis (RA) and osteoarthritis (OA) patients. Immunohistochemical staining showed that Notch-1, -2, and -3 were clearly expressed in the synovium from both RA and OA, whereas Notch-4 was only slightly detected. We further performed Western blotting with the same antibodies used in immunohistochemical staining. Notch-1 and -2 were strongly detected in both RA and OA, and the expression of Notch-3 was slightly detected, while there was no Notch-4 expression in both RA and OA synoviocytes. In contrast, all Notch homologues were strongly expressed in the synovium at the developmental stage obtained from the infant. These results indicate that the expression pattern of Notch among synovium from OA and RA patients differed from that of normal subjects.

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Section: Discussionmentioning

confidence: 99%

Expression of Notch homologues in the synovium of rheumatoid arthritis and osteoarthritis patients

Ishii

Nakazawa

Yoshino

et al. 2001

Rheumatology International

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“…Basic FGF, TNF␣, and TGF␤ are abundantly expressed in rheumatoid synovium, and are important cytokines involved in the regulation of cellular growth (4,5,32,33). Furthermore, bFGF and TGF␤ also activate the expression of several HOX genes (27,(34)(35)(36). Accordingly, we compared the effects of these cytokines on HOXD9 transcription in cotransfec- HOXD9 AND SYNOVIOCYTE PROLIFERATION tion assays in NIH3T3 fibroblasts and synoviocytes using a luciferase reporter construct carrying HCR, an autoregulatory element of HOXD9 promoter.…”

Section: Resultsmentioning

confidence: 99%

“…However, very little is known about its function in normal and pathologic adult tissues. In a series of recent studies, we have demonstrated preferential expression and activation of HOX genes in the rheumatoid synovium of adult patients, indicating that these genes are involved in the pathogenesis of arthritis (27,28). We previously reported that HOXD9 mRNA was characteristically expressed in RA synovium (27), and in this study we provide additional evidence that HOXD9 protein was detected in cultured rheumatoid synoviocytes.…”

Section: Discussionmentioning

confidence: 99%

“…NIH3T3 fibroblasts, OA synoviocytes, or RA synoviocytes were seeded into 6-well plates 24 hours before transfection, and the transfection was performed using the calcium phosphate precipitation method with the aid of the CellPhect transfection kit (Pharmacia Biotech, Uppsala, Sweden). Cells were cotransfected with 3 g of the reporter plasmid, 3 g of the expression construct or the control plasmid without an insert, and 1 g of pSV2Apap encoding human placental alkaline phosphatase as an internal control for normalizing transfection efficiently (27). Twenty-four hours after transfection, the cells were treated with recombinant human bFGF (Genzyme, Cambridge, MA), TNF␣ (Genzyme), or transforming growth factor ␤ (TGF␤) (Sigma, St. Louis, MO).…”

Section: Methodsmentioning

confidence: 99%

“…It is also known to be a potential transcription factor that not only autoregulates itself, but also transactivates other HOX genes as well as certain members of other families (25,26). We have recently demonstrated that HOXD9 is preferentially expressed in the proliferative synovium of RA patients (27). In another study in mice, we also found that the same HOX gene was expressed in embryonic joint tissues during early stages of joint formation, and that it was activated in arthritic joints of human T lymphotropic virus type I (HTLV-I) tax transgenic mice with RA-resembling arthropathy (28).…”

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confidence: 93%

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Potential role ofHOXD9 in synoviocyte proliferation

Khoa¹,

Nakazawa²,

Hasunuma³

et al. 2001

Arthritis & Rheumatism

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Expression of murineHOXD9 during embryonic joint patterning and in human T lymphotropic virus type Itax transgenic mice with arthropathy resembling rheumatoid arthritis

Khoa

Hasunuma

Kobata

et al. 1999

Arthritis & Rheumatism

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Objective. To characterize the expression of mu-rine HOXD9 during normal joint development and in arthritic joints of human T lymphotropic virus type I (HTLV-I) tax transgenic mice and the role of HTLV-I tax in HOXD9 expression. Methods. Expression of HOXD9, HOXD10, HOXD11, HOXD12, and HOXD13 genes in joint tissues at the ankle/foot regions of mouse embryos at day 10 to day 18 of gestation (E10-E18) and neonates within 10 days after birth was determined by reverse transcriptase-polymerase chain reaction and in situ reverse transcription methods. Adult synovial tissues from 5 HTLV-I tax transgenic mice with chronic poly-arthritis and 4 nontransgenic (normal) mice were also examined for expression of these HOXD genes. The effect of HTLV-I on HOXD9 expression in cultured synoviocytes was studied by in vitro infection and trans-fection experiments. Results. Expression of HOXD9 was detected in embryonic joints, preferentially on articular cartilage, only during the early stages of joint development (up to E15), whereas other HOXD genes were expressed throughout the embryonic and neonatal stages. In adult mice, transcripts of HOXD9 were specifically detected in synovial tissues from 4 of 5 arthritic mice, especially in the lining and sublining synovial cells, but not in synovial tissues of normal mice. Activation of HOXD9 was observed in cultured synoviocytes infected with HTLV-I in vitro as well as in those transfected with HTLV-I tax. Conclusion. Our findings suggest that HOXD9 is involved not only in the early stages of normal joint development, but may also be involved in the pathologic process of arthritis. HTLV-I tax appeared as an activa-tor of this HOX gene in cultured synoviocytes. The embryogenesis of synovial joints is of particular interest because analysis based on observations in normal subjects should expand our knowledge of the pathologic processes in various joint diseases. Joint embryogenesis is a complex process and is classically divided into 2 major morphologic events: formation of the cartilaginous anlages and subsequent joint formation. A number of studies have identified specific changes in certain cellular and molecular factors during joint development (1-5). The regulatory mechanisms of these processes, however, remain unclear. Homeobox (HOX) genes are known to encode transcriptional regulators involved in cell type-specific differentiation and control of the patterning of the body plan in vertebrates (6). A number of HOX genes, particularly the Drosophila AbdB-related (5-located) members of the HOXD complex (formerly known as HOX5 and later as HOX4), are thought to be involved in limb formation in mice and chicks (7-11). These genes are expressed in the developing limbs in domains that are spatially and temporally specific, but overlapping, depending on the developmental stage, and are thought to control segment identity and direct limb patterning and specification (12). Moreover, mutational analyses of

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Transcriptional regulation of the HOX4C gene by basic fibroblast growth factor on rheumatoid synovial fibroblasts

Cited by 9 publications

References 42 publications

Expression of Notch homologues in the synovium of rheumatoid arthritis and osteoarthritis patients

Expression of Notch homologues in the synovium of rheumatoid arthritis and osteoarthritis patients

Potential role ofHOXD9 in synoviocyte proliferation

Expression of murineHOXD9 during embryonic joint patterning and in human T lymphotropic virus type Itax transgenic mice with arthropathy resembling rheumatoid arthritis

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