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ABSTRACT: Osteitis pubis is a non-infective inflammation of the symphysis pubis, which is known to be associated with trauma, athletic exertion, urological or gynecological surgery, or with rheumatic conditions such as seronegative spondyloarthropathies. In this report, we describe a case of osteitis pubis whose symptoms were completely ameliorated following tooth extraction attributable to periodontitis. A 57-year-old female patient developed osteitis pubis, presenting with pain in the groin area with an elevated Creactive protein (CRP; 4.4 mg/dl) and radiological erosive changes in symphysis pubis. Prednisolone (5 mg/day) and etodolac were prescribed, but the patient's symptoms improved only partially and remained persistent. One year from the patient's first visit, three teeth were extracted due to severe chronic periodontitis, which she had been suffering from for years. Soon after the above tooth extraction, her symptoms appeared completely resolved, and the patient's CRP was decreased to nearly normal levels in 4 weeks. Human leukocyte antigen (HLA)-typing analysis revealed a positive result for HLA-A11, A24, and B54. Because HLA-B54 cross-reacts with HLA-B27, the patient's osteitis pubis was considered to be a form of reactive arthritis associated with periodontitis.
Clinical Rheumatology 03/2013; 32 Suppl 1:S63-5. · 2.00 Impact Factor
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Keiichiro Iida, Jun-Ichi Fukushi,
Yoshihiro Matsumoto,
Yoshinao Oda,
Yusuke Takahashi,
Toshifumi Fujiwara,
Yuko Fujiwara-Okada,
Mihoko Hatano,
Akira Nabashima,
Satoshi Kamura,
Yukihide Iwamoto
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ABSTRACT: Diverse functions of microRNAs (miRNAs), including effects on tumorigenesis, proliferation, and differentiation, have been reported, and several miRNAs have also been demonstrated to play an important role in apoptosis. In this study, we investigated the possible role that miRNAs may play in the development of chemoresistance in Ewing sarcoma/primitive neuroectodermal tumor (EWS).
We screened doxorubicin (Dox)-resistant EWS cells to identify any distinct miRNA sequences that may regulate the chemoresistance of EWS cells. The effects of miRNAs were evaluated using a chemosensitivity assay. The possible target genes of the miRNAs were predicted using a web-based prediction program.
We found miR-125b to be upregulated in two different Dox-resistant EWS cell lines. The upregulation of miR-125b was also confirmed in the EWS tumors having survived chemotherapy regimen which includes doxorubicin. When miR-125b was knocked down in EWS cells, both the Dox-resistant and parental cells showed an enhanced sensitivity to doxorubicin, which was associated with the upregulation of the pro-apoptotic molecules, p53 and Bak. Inversely, the overexpression of miR-125b in parental EWS cells resulted in enhanced drug resistance, not only to doxorubicin, but also to etoposide and vincristine.
Our findings suggest that miR-125b may play a role in the development of chemoresistance in EWS by suppressing the expression of the apoptotic mediators, such as p53 and Bak.
Cancer Cell International 01/2013; 13(1):21. · 1.97 Impact Factor
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ABSTRACT: The chromosomal translocation t(11;22)(q24;q12) yields the EWS-Fli1 fusion gene, which contributes to the development of Ewing Family Tumors (EFTs). Previous studies have shown the ability of EWS-Fli1 chimeric protein to silence p53 activity. Here we demonstrate that the introduction of EWS-Fli1 significantly inhibited p300-mediated acetylation of p53 at Lys-382 and depletion of EWS-Fli1 protein by small interfering RNAs (siRNA) in EFTs cells facilitated it in response to DNA damage. Furthermore, the deacetylation of p53 by EWS-Fli1 suppressed its transcriptional activity and enhanced mdm2-mediated p53 degradation. On the other hand, immunoprecipitation study shows that N-terminal region of EWS-Fli1 associated with histone deacetylase 1 (HDAC1) to forms a complex with p53. Knockdown of HDAC1, but not HDAC2 or HDAC3 protein restored the expression of p53 Lys-382 in EFTs cells. Overexpression of HDAC1 also significantly inhibited p53 transcriptional activity. Pharmacologic inhibitor of HDAC, trichostatin A (TSA) promoted p53-p300 interaction and recruitment of p53 Lys-382 to promoter regions of its target genes p21 and Puma, consequently inducing apoptosis and stabilizing the acetylation of p53 at Lys-382 together with the upregulation of p21 and Puma, which were impaired in EFTs cells after the knockdown of p53 expression. Our data indicate EWS-Fli1 might deacetylate p53 to inhibit its transcriptional function and protein stability via the recruitment of HDAC1. These results might elucidate a novel molecular mechanism about the abrogation of p53 pathway by EWS-Fli1 in EFTs pathogenesis.
Cancer letters 01/2012; 320(1):14-22. · 4.86 Impact Factor
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ABSTRACT: Hypophosphatasia is a rare inherited disorder characterized by a low serum alkaline phosphatase (ALP) activity and defective bone mineralization. Adult hypophosphatasia typically manifests in middle-age as a result of osteomalacia with recurrent stress fractures of the lower limb. However, considerable variation occurs in the clinical expression of hypophosphatasia, and no curative treatment has yet been established. We herein report a case of adult hypophosphatasia with painful calcific periarthritis, which showed improvement after surgical resection. A 32-year-old male was referred to our clinic complaining of pain in his elbows and knees. A painful subcutaneous mass was palpable on his right lateral epicondyle, where periarticular calcification was detected by plain radiography. The laboratory data showed a slight decrease in serum ALP activity and bone mineral density, and an elevation in the urinary phosphoethanolamine. Genomic DNA sequencing revealed an F310L mutation and a Y246H polymorphism in the tissue-nonspecific alkaline phosphatase gene, confirming the diagnosis of hypophosphatasia. The pain in the patient's right elbow was not responsive to nonsteroidal anti-inflammatory drugs, and triamcinolone diacetate was locally injected for treatment. His symptoms were ameliorated after the injection; however, they recurred in 3 months, and he became refractory to additional steroid injection. Surgical debridement of the calcified lesion was performed, and his symptoms were successfully ameliorated after the surgery.
Journal of Bone and Mineral Metabolism 12/2011; · 2.27 Impact Factor
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Toshifumi Fujiwara, Jun-ichi Fukushi,
Shunsaku Yamamoto,
Yoshihiro Matsumoto,
Nokitaka Setsu,
Yoshinao Oda,
Hisakata Yamada,
Seiji Okada,
Kosuke Watari,
Mayumi Ono,
Michihiko Kuwano,
Satoshi Kamura,
Keiichiro Iida,
Yuko Okada,
Mihoko Koga,
Yukihide Iwamoto
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ABSTRACT: Ewing sarcoma-primitive neuroectodermal tumor (EWS) is associated with the most unfavorable prognosis of all primary musculoskeletal tumors. The objective of the present study was to investigate whether tumor-associated macrophages (TAMs) affect the development of EWS. TAMs were isolated from mouse xenografts using CD11b magnetic beads and examined for their cytokine expression and osteoclastic differentiation. To evaluate the role of TAMs in xenograft formation, liposome-encapsulated clodronate was used to deplete TAMs in mice. Macrophage infiltration and tumor microvascular density were histologically evaluated in 41 patients with EWS, and association with prognosis was examined using Kaplan-Meier survival analysis. In mouse EWS xenografts, TAMs expressed higher concentrations of cytokines including interleukin-6, keratinocyte-derived chemokine, and monocyte chemotactic protein-1. TAMs were more capable than normal monocytes of differentiating into tartrate-resistant acid phosphatase-positive giant cells. Depleting macrophages using liposome-encapsulated clodronate significantly inhibited development of EWS xenografts. In human EWS samples, higher levels of CD68-positive macrophages were associated with poorer overall survival. In addition, enhanced vascularity, increase in the amount of C-reactive protein, and higher white blood cell counts were also associated with poor prognosis and macrophage infiltration. TAMs seem to enhance the progression of EWS by stimulating both angiogenesis and osteoclastogenesis. Further investigation of the behavior of TAMs may lead to development of biologically targeted therapies for EWS.
American Journal Of Pathology 09/2011; 179(3):1157-70. · 4.89 Impact Factor
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ABSTRACT: It was previously found that Th1 but not Th17 cells were predominant in the joints of rheumatoid arthritis (RA). To verify whether this is a unique feature of CD4 T cells in RA joints, we performed comparative flow cytometric analysis of CD4 T cells in RA and osteoarthritis (OA) joints.
Mononuclear cells were isolated from peripheral blood (PB), synovial membrane (SM), and synovial fluid (SF) from a total of 18 RA and 12 OA patients. The expression of surface molecules and cytokine production of CD4 T cells was examined by a flow cytometer.
Most CD4 T cells in RA joints expressed memory/activation markers, such as CD45RO, HLA-DR, and CD69. CCR5 was highly expressed on CD4 T cells in SF but not in PB or SM. With regard to Th17-related molecules, CD4 T cells expressing CCR6 were not enriched in either SF or SM. In contrast, CD161-positive cells were abundant in the joint, many of which, however, produced interferon-γ but not interleukin 17A. Virtually all T cells in OA joints, although much less numerous than in RA joints, expressed activation markers. Th1 cells were predominant in both OA and RA joints, while there were a few Th17 cells. The frequency of Th17 cells in the joint tended to be lower in OA than RA.
There was a quantitative but not qualitative difference in CD4 T cells, including the expression of activation markers and cytokine profiles, between RA and OA joints.
The Journal of Rheumatology 05/2011; 38(8):1569-75. · 3.69 Impact Factor
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Akari Tashiro,
Satoshi Takeuchi,
Takeshi Nakahara,
Junna Oba,
Jun Tsujita, Jun-ichi Fukushi,
Hiromaro Kiryu,
Yoshinao Oda,
Lining Xie,
Xiaofeng Yan,
Masakazu Takahara,
Yoichi Moroi,
Masutaka Furue
The Journal of Dermatology 11/2010; 37(11):995-7. · 1.49 Impact Factor
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ABSTRACT: As invasive medical procedures can induce permanent heterotopic ossification in fibrodysplasia ossificans progressiva (FOP), caution should be exercised in clinical practice. The present study was conducted to examine the characteristics of the great toe deformity in patients with FOP, which may lead to an early diagnosis of this condition.
The subjects consisted of 31 feet from 16 FOP patients (8 males, 8 females) with an average age of 17.3 years (range 1-47 years) at the time of this study. Gross and radiographic findings, including the hallux valgus angles (HVA), intermetatarsal angles (IMA), and the deformity of the proximal phalanx and metatarsal bone, were examined.
Of the 31 feet, 29 (93.5%) showed several degrees of great toe deformity. A shortened great toe was the typical gross finding and was observed in 20 feet (64.5%). The mean HVA and IMA were 19.7° and 8.5°, respectively; and 22 (71.0%) feet satisfied the radiographic definition of hallux valgus (HVA ≥ 20° or IMA ≥ 10°). The proximal phalanx was consistently shortened but morphologically dissimilar from case to case. The metatarsal bone was also shortened and sharpened to the medial side, deviating the proximal phalanx laterally from the metatarsal axis. Fusion between the distal and proximal phalanx occurred with advancing age. Only two feet in one patient showed no obvious deformity of the great toe.
A shortened great toe and hallux valgus were frequently found in patients with FOP. Shortening and sharpening of the proximal phalanx and metatarsal bone consistently existed and contributed to the great toe deformity. These findings were thought to exist from birth and may be a key to an early diagnosis.
Journal of Orthopaedic Science 11/2010; 15(6):804-9. · 0.84 Impact Factor
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Yoshihiro Matsumoto,
Yuko Okada, Jun-Ichi Fukushi,
Satoshi Kamura,
Toshifumi Fujiwara,
Keiichiro Iida,
Mihoko Koga,
Shuichi Matsuda,
Katsumi Harimaya,
Akio Sakamoto,
Yukihide Iwamoto
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ABSTRACT: Giant cell tumors (GCTs) of bone are primary benign bone tumors that are characterized by a high number of osteoclast-like multinuclear giant cells (MNCs). Recent studies suggest that the spindle-shaped stromal cells in GCTs are tumor cells, while monocyte-like cells and MNCs are reactive osteoclast precursor cells (OPCs) and osteoclasts (OCs), respectively. In this study, we investigated the pathogenesis of osteoclastic bone destruction in GCTs by focusing on the role of the vascular endothelial growth factor (VEGF)-Flt-1 (type-1 VEGF receptor)-focal adhesion kinase (FAK) pathway.
The motility of OPCs cells was assessed by a chemotaxis assay and the growth of OPCs was examined using a cell proliferation assay. The expression of VEGF and activation of Flt-1 and FAK in clinical GCT samples and in OPCs were detected by immunohistochemistry and immunoblotting. The correlation between the expression levels of activated Flt-1 and FAK and clinical stages of GCTs was investigated by immunohistochemistry.
In GCT samples, CD68, a marker of OPCs and OCs, co-localized with Flt-1. Conditioned media from GCT tissue (GCT-CM) enhanced the chemotaxis and proliferation of OPCs. GCT-CM also stimulated FAK activation in OPCs in vitro. Moreover, there was a correlation between the clinical stage of GCTs and the expression of tyrosine-phosphorylated Flt-1 and FAK.
Our results suggest that the VEGF-Flt-1-FAK pathway is involved in the pathogenesis of bone destruction of GCTs.
Journal of Orthopaedic Surgery and Research 11/2010; 5:85.
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ABSTRACT: Increasing evidence indicates that heparan sulfate (HS) is an integral component of many morphogen signaling pathways. However, its mechanisms of action appear to be diverse, depending on the type of morphogen and the developmental contexts. To define the function of HS in skeletal development, we conditionally ablated Ext1, which encodes an essential glycosyltransferase for HS synthesis, in limb bud mesenchyme using the Prx1-Cre transgene. These conditional Ext1 mutant mice display severe limb skeletal defects, including shortened and malformed limb bones, oligodactyly, and fusion of joints. In developing limb buds of mutant mice, chondrogenic differentiation of mesenchymal condensations is delayed and impaired, whereas the area of differentiation is diffusely expanded. Correspondingly, the distribution of both bone morphogenic protein (BMP) signaling domains and BMP2 immunoreactivity in the mutant limb mesenchyme is broadened and diffuse. In micromass cultures, chondrogenic differentiation of mutant chondrocytes is delayed, and the responsiveness to exogenous BMPs is attenuated. Moreover, the segregation of the pSmad1/5/8-expressing chondrocytes and fibronectin-expressing perichondrium-like cells surrounding chondrocyte nodules is disrupted in mutant micromass cultures. Together, our results show that HS is essential for patterning of limb skeletal elements and that BMP signaling is one of the major targets for the regulatory role of HS in this developmental context.
Journal of Biological Chemistry 06/2010; 285(25):19227-34. · 4.77 Impact Factor
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ABSTRACT: Increasing evidence indicates that heparan sulfate (HS) is an integral component of many morphogen signaling pathways. However,
its mechanisms of action appear to be diverse, depending on the type of morphogen and the developmental contexts. To define
the function of HS in skeletal development, we conditionally ablated Ext1, which encodes an essential glycosyltransferase
for HS synthesis, in limb bud mesenchyme using the Prx1-Cre transgene. These conditional Ext1 mutant mice display severe limb
skeletal defects, including shortened and malformed limb bones, oligodactily, and fusion of joints. In developing limb buds
of mutant mice, chondrogenic differentiation of mesenchymal condensations is delayed and impaired, whereas the area of differentiation
is diffusely expanded. Correspondingly, the distribution of both BMP signaling domains and BMP2 immunoreactivity in the mutant
limb mesenchyme is broadened and diffuse. In micromass cultures, chondrogenic differentiation of mutant chondrocytes is delayed
and the responsiveness to exogenous BMPs is attenuated. Moreover, the segregation of the pSmad1/5/8-expressing chondrocytes
and fibronectin-expressing perichondrium-like cells surrounding chondrocyte nodules is totally disrupted in mutant micromass
cultures. Together, our results show that HS is essential for patterning of limb skeletal elements, and that BMP signaling
is one of the major targets for the regulatory role of HS in this developmental context.
Journal of Biological Chemistry 04/2010; · 4.77 Impact Factor
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ABSTRACT: A 62-year-old male with a 10-year history of seropositive rheumatoid arthritis (RA) developed gynecomastia 8 months after beginning oral low-dose methotrexate (MTX) therapy. Two months after folate supplementation, the gynecomastia symptoms improved. Gynecomastia associated with low-dose MTX is a rare occurrence, with only nine cases previously reported in the literature. This is the first report showing folate supplementation to be effective against gynecomastia following low-dose MTX. Although it occurs infrequently, gynecomastia associated with low-dose MTX therapy should be considered in male patients with RA.
Rheumatology International 08/2009; 30(10):1371-2. · 1.88 Impact Factor
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Marcia Dawson,
Zebin Xia,
Gang Liu,
Mao Ye,
Joseph Fontana,
Lulu Farhana,
Bhamik Patel,
Sankari Arumugarajah,
Mohammad Bhuiyan,
Xiao-kun Zhang, [......],
Tomas Mustelin,
Lutz Tautz,
Ying Su,
Danni Harris,
Nahid Waleh,
Peter Hobbs,
Ling Jong,
Wan-Ru Chao,
Leonard Schiff,
Brahma Sani
Journal of Medicinal Chemistry 10/2008; · 4.80 Impact Factor
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Marcia I. Dawson,
Zebin Xia,
Gang Liu,
Mao Ye,
Joseph A. Fontana,
Lulu Farhana,
Bhamik B. Patel,
Sankari Arumugarajah,
Mohammad Bhuiyan,
Xiao-Kun Zhang, [......],
Tomas Mustelin,
Lutz Tautz,
Ying Su,
Danni L. Harris,
Nahid Waleh,
Peter D. Hobbs,
Ling Jong,
Wan-ru Chao,
Leonard J. Schiff,
Brahma P. Sani
09/2008;
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ABSTRACT: In early postnatal mouse skin, the NG2 proteoglycan is expressed in the subcutis, the dermis, the outer root sheath of hair follicles, and the basal keratinocyte layer of the epidermis. With further development, NG2 is most prominently expressed by stem cells in the hair follicle bulge region, as also observed in adult human skin. During telogen and anagen phases of the adult hair cycle, NG2 is also found in stem cell populations that reside in dermal papillae and the outer root sheaths of hair follicles. Ablation of NG2 produces alterations in both the epidermis and subcutis layers of neonatal skin. Compared with wild type, the NG2 null epidermis does not achieve its full thickness due to reduced proliferation of basal keratinocytes that serve as the stem cell population in this layer. Thickening of the subcutis is also delayed in NG2 null skin due to deficiencies in the adipocyte population.
Journal of Histochemistry and Cytochemistry 04/2008; 56(3):295-303. · 2.72 Impact Factor
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ABSTRACT: Recent animal studies have revealed critical roles of interleukin (IL)17, which is produced by a newly identified subset of helper T cells, Th17 cells, in the development of autoimmune diseases including arthritis. However, in human rheumatoid arthritis (RA), detailed characteristics and the prevalence of Th17 cells are unclear.
Peripheral blood mononuclear cells (PBMC) were obtained from 123 patients with RA and 28 healthy controls. Mononuclear cells were also prepared from synovial membrane or synovial fluid of 12 patients with RA. IL17 (IL17A) positive T cells were identified by a flow cytometer after ex vivo stimulation with phorbol myristate acetate and ionomycin. Disease activity was assessed with the 28-joint Disease Activity Score (DAS28).
IL17 positive cells were detected in CD45RO+ CD4 T cells. Most IL17 positive T cells produced neither interferon (IFN)gamma nor IL4, but tumour necrosis factor (TNF)alpha similar to murine Th17 cells. The frequency of Th17 cells was neither increased in RA nor correlated with DAS28. Unexpectedly, the frequency of Th17 cells was significantly decreased in the joints compared with PBMC of the same patients with RA, whereas Th1 cells were more abundant in the joints than in PBMC.
We could not obtain evidence that positively supports predominance of Th17 cells in RA. Further careful investigation is necessary before clinical application of IL17-targeting therapy.
Annals of the rheumatic diseases 01/2008; 67(9):1299-304. · 8.11 Impact Factor
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Marcia I Dawson,
Zebin Xia,
Gang Liu,
Mao Ye,
Joseph A Fontana,
Lulu Farhana,
Bhamik B Patel,
Sankari Arumugarajah,
Mohammad Bhuiyan,
Xiao-Kun Zhang, [......],
Tomas Mustelin,
Lutz Tautz,
Ying Su,
Danni L Harris,
Nahid Waleh,
Peter D Hobbs,
Ling Jong,
Wan-Ru Chao,
Leonard J Schiff,
Brahma P Sani
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ABSTRACT: Apoptotic and antiproliferative activities of small heterodimer partner (SHP) nuclear receptor ligand (E)-4-[3'-(1-adamantyl)-4'-hydroxyphenyl]-3-chlorocinnamic acid (3-Cl-AHPC), which was derived from 6-[3'-(1-adamantyl)-4'-hydroxyphenyl]-2-naphthalenecarboxylic acid (AHPN), and several carboxyl isosteric or hydrogen bond-accepting analogues were examined. 3-Cl-AHPC continued to be the most effective apoptotic agent, whereas tetrazole, thiazolidine-2,4-dione, methyldinitrile, hydroxamic acid, boronic acid, 2-oxoaldehyde, and ethyl phosphonic acid hydrogen bond-acceptor analogues were inactive or less efficient inducers of KG-1 acute myeloid leukemia and MDA-MB-231 breast, H292 lung, and DU-145 prostate cancer cell apoptosis. Similarly, 3-Cl-AHPC was the most potent inhibitor of cell proliferation. 4-[3'-(1-adamantyl)-4'-hydroxyphenyl]-3-chlorophenyltetrazole, (2E)-5-{2-[3'-(1-adamantyl)-2-chloro-4'-hydroxy-4-biphenyl]ethenyl}-1H-tetrazole, 5-{4-[3'-(1-adamantyl)-4'-hydroxyphenyl]-3-chlorobenzylidene}thiazolidine-2,4-dione, and (3E)-4-[3'-(1-adamantyl)-2-chloro-4'-hydroxy-4-biphenyl]-2-oxobut-3-enal were very modest inhibitors of KG-1 proliferation. The other analogues were minimal inhibitors. Fragment-based QSAR analyses relating the polar termini with cancer cell growth inhibition revealed that length and van der Waals electrostatic surface potential were the most influential features on activity. 3-Cl-AHPC and the 3-chlorophenyltetrazole and 3-chlorobenzylidenethiazolidine-2,4-dione analogues were also able to inhibit SHP-2 protein-tyrosine phosphatase, which is elevated in some leukemias. 3-Cl-AHPC at 1.0 microM induced human microvascular endothelial cell apoptosis but did not inhibit cell migration or tube formation.
Journal of Medicinal Chemistry 06/2007; 50(11):2622-39. · 5.25 Impact Factor
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ABSTRACT: Previous work has demonstrated the ability of the NG2 proteoglycan, a component of microvascular pericytes, to stimulate endothelial cell motility and morphogenesis. This function of NG2 depends on formation of a complex with galectin-3 and alpha3beta1 integrin to stimulate integrin-mediated transmembrane signaling. In addition, the co-expression of galectin-3 and NG2 in A375 melanoma cells suggests that the malignant properties of these cells may be affected by interaction between the two molecules. Here, we extend the theme of co-expression and interaction of NG2 and galectin-3 to human glioma cells. We also establish a molecular basis for the NG2/galectin-3 interaction. The C-terminal carbohydrate recognition domain of galectin-3 is responsible for binding to the NG2 core protein. Within the NG2 extracellular domain, the membrane-proximal D3 segment of the proteoglycan contains the primary binding site for interaction with galectin-3. The interaction between galectin-3 and NG2 is a carbohydrate-dependent one mediated by N-linked rather than O-linked oligosaccharides within the D3 domain of the NG2 core protein. These studies establish a foundation for attempts to reduce the aggressive properties of tumor cells by disrupting the NG2/galectin-3 interaction.
Journal of Cellular Biochemistry 06/2006; 98(1):115-27. · 2.87 Impact Factor
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ABSTRACT: Protein kinase C (PKC)-alpha phosphorylation of recombinant NG2 cytoplasmic domain and phorbol ester-induced PKC-dependent phosphorylation of full-length NG2 expressed in U251 cells are both blocked by mutation of Thr(2256), identifying this residue as a primary phosphorylation site. In untreated U251/NG2 cells, NG2 is present along with ezrin and alpha(3)beta(1) integrin in apical cell surface protrusions. Phorbol ester treatment causes redistribution of all three components to lamellipodia, accompanied by increased cell motility. U251 cells expressing NG2 with a valine substitution at position 2256 are resistant to phorbol ester treatment: NG2 remains in membrane protrusions and cell motility is unchanged. In contrast, NG2 with a glutamic acid substitution at position 2256 redistributes to lamellipodia even without phorbol ester treatment, rendering transfected U251 cells spontaneously motile. PKC-alpha-mediated NG2 phosphorylation at Thr(2256) is therefore a key step for initiating cell polarization and motility.
Journal of Biological Chemistry 01/2005; 279(53):55262-70. · 4.77 Impact Factor
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ABSTRACT: The NG2 proteoglycan is expressed by microvascular pericytes in newly formed blood vessels. We have used in vitro and in vivo models to investigate the role of NG2 in cross-talk between pericytes and endothelial cells (EC). Binding of soluble NG2 to the EC surface induces cell motility and multicellular network formation in vitro and stimulates corneal angiogenesis in vivo. Biochemical data demonstrate the involvement of both galectin-3 and alpha3beta1 integrin in the EC response to NG2 and show that NG2, galectin-3, and alpha3beta1 form a complex on the cell surface. Transmembrane signaling via alpha3beta1 is responsible for EC motility and morphogenesis in this system. Galectin-3-dependent oligomerization may potentiate NG2-mediated activation of alpha3beta1. In conjunction with recent studies demonstrating the early involvement of pericytes in angiogenesis, these data suggest that pericyte-derived NG2 is an important factor in promoting EC migration and morphogenesis during the early stages of neovascularization.
Molecular Biology of the Cell 09/2004; 15(8):3580-90. · 4.94 Impact Factor
