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ABSTRACT: OBJECTIVES/HYPOTHESIS: To test the osteoregenerative potential and dosing of bone morphogenetic protein-2 (BMP-2)-impregnated biomimetic scaffolds in a rat model of a mandibular defect. STUDY DESIGN: Prospective study using an animal model. METHODS: Varied doses of BMP-2 (0.5, 1, 0.5, 0.5 in microspheres, 5, and 15 μg) were absorbed onto a biomimetic scaffold. Scaffolds were then implanted into marginal mandibular defects in rats. Blank scaffolds and unfilled defects were used as negative controls. Two months postoperatively, bone healing was analyzed with microcomputerized tomography (microCT). RESULTS: MicroCT analysis demonstrated that all doses of BMP-2 induced successful healing of marginal mandibular defects in a rat mandible. Increasing doses of BMP-2 on the scaffolds produced increased tissue healing, with 15 μg demonstrating significantly more healing than all other dosing (P < .01). CONCLUSIONS: BMP-2-impregnated biomimetic scaffolds successfully induce bone healing in a marginal mandibular defect in the rat. Percentage healing of defect, percentage of bone within healed tissue, and total bone volume are all a function of BMP-2 dosing. There appears to be an optimal dose of 5 μg beyond which there is no increase in bone volume. LEVEL OF EVIDENCE: NA Laryngoscope, 2012.
The Laryngoscope 04/2013; · 1.75 Impact Factor
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ABSTRACT: Osteonecrosis of the jaw (ONJ) is a well-recognized complication of antiresorptive medications, such as bisphosphonates (BPs). Although ONJ is most common after tooth extractions in patients receiving high dose BPs, many patients do not experience oral trauma. Animal models utilizing tooth extractions and high BP doses recapitulate several clinical, radiographic and histologic findings of ONJ. We and others have reported on rat models of ONJ utilizing experimental dental disease in the absence of tooth extraction. These models emphasize the importance of dental infection/inflammation for ONJ development. Here, we extend our original report in the rat, and present a mouse model of ONJ in the presence of dental disease. Mice were injected with high dose zoledronic acid and pulpal exposure of mandibular molars was performed to induce periapical disease. After 8 weeks, quantitative and qualitative radiographic and histologic analyses of mouse mandibles were executed. Periapical lesions were larger in vehicle- vs. BP treated mice. Importantly, radiographic features resembling clinical ONJ, including thickening of the lamina dura, periosteal bone deposition and increased trabecular density, were seen in the drilled site of BP treated animals. Histologically, osteonecrosis, periosteal thickening, periosteal bone apposition, epithelial migration and bone exposure were present in the BP treated animals in the presence of periapical disease. No difference in TRAP+ cell numbers was observed, but round, detached, and removed from the bone surface cells were present in BP animals. Although 88% of the BP animals showed areas of osteonecrosis in the dental disease site, only 33% developed bone exposure, suggesting that osteonecrosis precedes bone exposure. Our data further emphasize the importance of dental disease in ONJ development, provide qualitative and quantitative measures of ONJ, and present a novel mouse ONJ model in the absence of tooth extraction that should be useful in further exploring ONJ pathophysiological mechanisms. © 2013 American Society for Bone and Mineral Research.
Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 02/2013; · 6.04 Impact Factor
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ABSTRACT: ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Dental x-rays and risk of meningioma. Claus EB, Calvocoressi L, Bondy ML, Schildkraut JM, Wiemels JL, Wrensch M. Cancer 2012. Epub ahead of print. REVIEWERS: Sotirios Tetradis, DDS, PhD, Stuart C. White, DDS, PhD, Susan K. Service, MS PURPOSE/QUESTION: To examine whether there is an association between age at receipt or frequency of dental radiographs and intracranial meningioma SOURCE OF FUNDING: The National Institutes of Health (R01 grants CA109468, CA109461, CA109745, CA108473, and CA109475), the Brain Science Foundation (nonprofit), and the Meningioma Mommas (nonprofit) TYPE OF STUDY/DESIGN: Case-control study LEVEL OF EVIDENCE: Level 2: Limited-quality, patient-oriented evidence STRENGTH OF RECOMMENDATION GRADE: Not applicable.
The journal of evidence-based dental practice 09/2012; 12(3):174-7.
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ABSTRACT: Segmental mandibular defects can result after the treatment of various pathologic processes, including osteoradionecrosis, tumor resection, or fracture nonunion with sequestration. The variety of etiologies and the frequency of occurrence make the reconstruction of segmental mandibular defects a topic of significant interest. Despite these incentives, a well-established small-animal model of the segmental mandibulectomy, including composite resection, does not exist. The objective of this study is the creation of a reliable animal model that can be used to study the reconstruction of en bloc mandibular defects. Surgical techniques and an array of reconstructive options are described.
Description of an animal model.
Animal laboratory at a quaternary care university medical center.
We present an Animal Research Oversight Committee-approved prospective analysis of survival operations in the rat model. A detailed, stepwise description of surgical technique and relevant intraoperative anatomy is presented. Postoperative management, early pitfalls, surgical complications, and future applications are discussed.
A total of 72 operations were performed by a single individual between July and October 2010. Two intraoperative and 9 postoperative complications were recognized. There were 6 orocutaneous fistulas, 2 abscesses, and 1 seroma. There were 4 fatalities, which were attributed to anesthetic complications (2, intraoperative), hematoma formation (1, postoperative), and foreign-body aspiration (1, postoperative).
This novel animal model reliably replicates the en bloc segmental mandibular defects seen in our patient population and can be manipulated to achieve a wide variety of research objectives.
Otolaryngology Head and Neck Surgery 01/2012; 146(6):932-7. · 1.72 Impact Factor
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ABSTRACT: Conventional radiographs provide important information for dental disease diagnosis. However, they represent 2-D images of 3-D objects with significant structure superimposition and unpredictable magnification. Cone beam computed tomography, however, allows true 3-D visualization of the dentoalveolar structures, avoiding major limitations of conventional radiographs. Cone beam computed tomography images offer great advantages in disease detection for selected patients. The authors discuss cone beam computed tomography applications in dental disease diagnosis, reviewing the pertinent literature when available.
Texas dental journal 07/2011; 128(7):620-8.
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ABSTRACT: In hyperlipidemia, oxidized lipids accumulate in vascular tissues and trigger atherosclerosis. Such lipids also deposit in bone tissues, where they may promote osteoporosis. We found previously that oxidized lipids attenuate osteogenesis and that parathyroid hormone (PTH) bone anabolism is blunted in hyperlipidemic mice, suggesting that osteoporotic patients with hyperlipidemia may develop resistance to PTH therapy. To determine if oxidized lipids account for this PTH resistance, we blocked lipid oxidation products in hyperlipidemic mice with an ApoA-I mimetic peptide, D-4F, and the bone anabolic response to PTH treatment was assessed. Skeletally immature Ldlr(-/-) mice were placed on a high-fat diet and treated with D-4F peptide and/or with intermittent PTH(1-34) injections. As expected, D-4F attenuated serum lipid oxidation products and tissue lipid deposition induced by the diet. Importantly, D-4F treatment attenuated the adverse effects of dietary hyperlipidemia on PTH anabolism by restoring micro-computed tomographic parameters of bone quality-cortical mineral content, area, and thickness. D-4F significantly reduced serum markers of bone resorption but not bone formation. PTH and D-4F, together but not separately, also promoted bone anabolism in an alternative model of hyperlipidemia, Apoe(-/-) mice. In normolipemic mice, D-4F cotreatment did not further enhance the anabolic effects of PTH, indicating that the mechanism is through its effects on lipids. These findings suggest that oxidized lipids mediate hyperlipidemia-induced PTH resistance in bone through modulation of bone resorption.
Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 06/2011; 26(6):1197-206. · 6.04 Impact Factor
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Jared S Johnson,
Vicente Meliton,
Woo Kyun Kim,
Kwang-Bok Lee,
Jeffrey C Wang,
Khanhlinh Nguyen,
Dongwon Yoo,
Michael E Jung,
Elisa Atti, Sotirios Tetradis,
Renata C Pereira,
Clara Magyar,
Taya Nargizyan,
Theodore J Hahn,
Francine Farouz,
Scott Thies,
Farhad Parhami
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ABSTRACT: Stimulation of bone formation by osteoinductive materials is of great clinical importance in spinal fusion surgery, repair of bone fractures, and in the treatment of osteoporosis. We previously reported that specific naturally occurring oxysterols including 20(S)-hydroxycholesterol (20S) induce the osteogenic differentiation of pluripotent mesenchymal cells, while inhibiting their adipogenic differentiation. Here we report the characterization of two structural analogues of 20S, Oxy34 and Oxy49, which induce the osteogenic and inhibit the adipogenic differentiation of bone marrow stromal cells (MSC) through activation of Hedgehog (Hh) signaling. Treatment of M2-10B4 MSC with Oxy34 or Oxy49 induced the expression of osteogenic differentiation markers Runx2, Osterix (Osx), alkaline phosphatase (ALP), bone sialoprotein (BSP), and osteocalcin (OCN), as well as ALP enzymatic activity and robust mineralization. Treatment with oxysterols together with PPARγ activator, troglitazone (Tro), inhibited mRNA expression for adipogenic genes PPARγ, LPL, and aP2, and inhibited the formation of adipocytes. Efficacy of Oxy34 and Oxy49 in stimulating bone formation in vivo was assessed using the posterolateral intertransverse process rat spinal fusion model. Rats receiving collagen implants with Oxy 34 or Oxy49 showed comparable osteogenic efficacy to BMP2/collagen implants as measured by radiography, MicroCT, and manual inspection. Histological analysis showed trabecular and cortical bone formation by oxysterols and rhBMP2 within the fusion mass, with robust adipogenesis in BMP2-induced bone and significantly less adipocytes in oxysterol-induced bone. These data suggest that Oxy34 and Oxy49 are effective novel osteoinductive molecules and may be suitable candidates for further development and use in orthopedic indications requiring local bone formation.
Journal of Cellular Biochemistry 06/2011; 112(6):1673-84. · 2.87 Impact Factor
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ABSTRACT: Nell-1 is a growth factor required for normal skeletal development and expression of extracellular matrix proteins required for bone and cartilage cell differentiation. We identified the transcription factor nuclear factor of activated T cells (Nfatc2) as a primary response gene of Nell-1 through a microarray screen, with validation using real-time polymerase chain reaction (PCR). We investigated the effects of recombinant Nell-1 protein on the chondrogenic cell line ATDC5 and primary mouse chondrocytes. The osteochondral transcription factor Runx2 was investigated as a possible intermediary between Nell-1 and Nfatc2 using adenoviral overexpression of wild-type and dominant-negative Runx2. Nell-1 transiently induced both transcription and translation of Nfatc2, an effect inhibited by transduction of dominant-negative Runx2, suggesting that Runx2 was necessary for Nfatc2 induction. Differentiation assays revealed inhibitory effects of Nell-1 on ATDC5 cells. Although proliferation was unaffected, expression of chondrocyte-specific genes was decreased, and cartilage nodule formation and proteoglycan accumulation were suppressed. siRNA knockdown of Nfatc2 significantly reversed these inhibitory effects. To elucidate the relationship between Nell-1, Runx2, and Nfatc2 in vivo, their presence and distribution were visualized in femurs of wild-type and Nell1-deficient mice at both neonatal and various developmental stages using immunohistochemistry. All three proteins colocalized in the perichondrium of wild-type femurs but stained weakly or were completely absent in Nell1-deficient femurs at neonatal stages. Thus Nfatc2 likely plays an important role in Nell-1-mediated osteochondral differentiation in vitro and in vivo. To our knowledge, this is the first demonstration that Nfatc2 is a primary response gene of Nell-1.
Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 06/2011; 26(6):1230-41. · 6.04 Impact Factor
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ABSTRACT: Bisphosphonates (BPs) are medications used commonly to treat primary and metastatic bone cancer, as well as osteoporosis. Although BPs improve bone mineral density, reduce fracture risk, and reduce hypercalcemia of malignancy, some patients develop BP-related osteonecrosis of the jaws (BRONJ). This devastating complication is defined as clinically exposed bone in the maxillofacial region for more than 8 weeks. Despite an increasing number of BRONJ cases since first reported, the disease pathophysiology remains largely unknown. Since published studies suggest a significant role for dental disease in the pathophysiology of BRONJ, we developed a BRONJ animal model where aggressive periodontal disease is induced by ligature placement around the crown of the right maxillary first molar in the presence of vehicle (veh) or zoledronic acid (ZA), a potent BP. Ligature placement induced significant alveolar bone loss, which was attenuated by ZA treatment. Osteonecrosis was observed associated with ligature-induced periodontitis in the ZA-treated group. This was seen as sequestration and extensive periosteal alveolar bone formation on micro-computed tomography (µCT) in the ligated site of BP-treated animals. Histologic examination confirmed these findings, seen as necrotic bone with diffuse loss of osteocytes and empty lacunae, rimming of the necrotic bone by squamous epithelium and inflammation, and exposure to the oral cavity. Importantly, the rat lesions were strikingly similar to those of BRONJ patients. Our data suggest that dental disease and potent BP therapy are sufficient for BRONJ development in the rat.
Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 02/2011; 26(8):1871-82. · 6.04 Impact Factor
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ABSTRACT: Osteoporosis, which contributes to morbidity and mortality, often coexists with cardiovascular disease, especially atherosclerosis. We have reported recently that in vitro exposure of human T-lymphocytes to oxidized lipids induced expression of a key osteoclastogenic cytokine, receptor activator of NF-κB ligand (RANKL). Our previous studies have shown that mice fed an atherogenic high-fat diet developed osteopenia and that bone marrow preosteoclasts from these hyperlipidemic mice have increased osteoclastic potential. To investigate the role of T-lymphocytes in the diet-induced bone loss, C57BL/6 mice were fed either chow or a high-fat diet, and bone parameters and T-lymphocyte activation were assessed at 6 and 11 months. Consistent with our previous findings, peripheral quantitative computed tomographic (pQCT) analysis showed that mice in the high-fat group had lower bone mineral content than mice in the chow group. Furthermore, histomorphometric analysis showed decreased structural parameters in the high-fat group. Coculture studies showed that bone marrow cells isolated from the high-fat group, which contained increased levels of activated memory T-lymphocytes compared with bone marrow cells from the chow mice, supported osteoclastic differentiation of RAW 264.7 cells. Additionally, RANKL expression was upregulated significantly in the T-lymphocytes isolated from the bone marrow of the high-fat group. Splenic T-lymphocytes isolated from the high-fat group also had increased expression of transcripts for the receptor for oxidized lipids (LOX-1) as well as for inflammatory and osteoclastogenic cytokines, including RANKL, interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), IL-1β, and interferon γ (IFN-γ). Together these findings suggest that T-lymphocytes play a key role in the osteoclastogenesis induced by a high-fat diet and may contribute to the bone loss associated with diet-induced osteopenia.
Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 11/2010; 25(11):2460-9. · 6.04 Impact Factor
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Neurosurgery 08/2010; 67(2):E521. · 2.79 Impact Factor
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Journal of oral and maxillofacial surgery: official journal of the American Association of Oral and Maxillofacial Surgeons 02/2010; 68(5):959-63. · 1.58 Impact Factor
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ABSTRACT: Abstract Background Resorbable bone hemostasis materials, oxidized regenerated cellulose (ORC) and microfibrillar collagen (MFC), remain at the site of application for up to 8 weeks and may impair osteogenesis. Our experimental study compared the effect of a water-soluble alkylene oxide copolymer (AOC) to ORC and MFC versus no hemostatic material on early bone healing. Methods Two circular 2.7 mm non-critical defects were made in each tibia of 12 rabbits. Sufficient AOC, ORC or MFC was applied to achieve hemostasis, and effectiveness recorded. An autologous blood clot was applied to control defects. Rabbits were sacrificed at 17 days, tibiae excised and fixed. Bone healing was quantitatively measured by micro-computed tomography (micro-CT) expressed as fractional bone volume, and qualitatively assessed by histological examination of decalcified sections. Results Hemostasis was immediate after application of MFC and AOC, after 1-2 minutes with ORC, and >5 minutes for control. At 17 days post-surgery, micro-CT analysis showed near-complete healing in control and AOC groups, partial healing in the ORC group and minimal healing in the MFC group. Fractional bone volume was 8 fold greater in the control and AOC groups than in the MFC group (0.42 ± 0.06, 0.40 ± 0.03 vs 0.05 ± 0.01, P < 0.001) and over 1.5-fold greater than in the ORC group (0.25 ± 0.03, P < 0.05). By histology, MFC remained at the application site with minimal healing at the defect margins and early fibrotic tissue within the defect. ORC-treated defects showed partial healing but with early fibrotic tissue in the marrow space. Conversely, control and AOC-treated defects demonstrated newly formed woven bone rich in cellular activity with no evidence of AOC remaining at the application site. Conclusions Early healing appeared to be impaired by the presence of MFC and impeded by the presence of ORC. In contrast, AOC did not inhibit bone healing and suggest that AOC may be a better bone hemostatic material for procedures where bony fusion is critical and immediate hemostasis required.
BMC Surgery. 01/2010;
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ABSTRACT: Cone beam computed tomography imaging represents a paradigm shift for enhancing diagnosis and treatment planning. Questions regarding cone beam computed tomography's associated legal responsibility are addressed, including cone beam computed tomography necessity, recognition of pathosis in the scan's entire volume, adequate training, informed consent and/or refusal and current court status of cone beam computed tomography. Judicious selection and prudent use of cone beam computed tomography technology to protect and promote patient safety and efficacious treatment complies with the standard of care.
Journal of the California Dental Association 01/2010; 38(1):49-56.
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ABSTRACT: A radiological examination is an essential part of the diagnosis and management of temporomandibularjoint disease. Accurate evaluation of the TMJ has been difficult due to the superimposition of other structure in conventional radiographs. Cone beam computed tomography provides precise imaging of TMJ anatomy without superimposition and distortion. The CBCT's preciseness enables practitioners to better identify problems, as well for other strategies. Common conditions of the TMJ in which CBCT plays a role are discussed.
Journal of the California Dental Association 01/2010; 38(1):33-9.
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Journal of the California Dental Association 01/2010; 38(1):24-6.
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ABSTRACT: Resorbable bone hemostasis materials, oxidized regenerated cellulose (ORC) and microfibrillar collagen (MFC), remain at the site of application for up to 8 weeks and may impair osteogenesis. Our experimental study compared the effect of a water-soluble alkylene oxide copolymer (AOC) to ORC and MFC versus no hemostatic material on early bone healing.
Two circular 2.7 mm non-critical defects were made in each tibia of 12 rabbits. Sufficient AOC, ORC or MFC was applied to achieve hemostasis, and effectiveness recorded. An autologous blood clot was applied to control defects. Rabbits were sacrificed at 17 days, tibiae excised and fixed. Bone healing was quantitatively measured by micro-computed tomography (micro-CT) expressed as fractional bone volume, and qualitatively assessed by histological examination of decalcified sections.
Hemostasis was immediate after application of MFC and AOC, after 1-2 minutes with ORC, and >5 minutes for control. At 17 days post-surgery, micro-CT analysis showed near-complete healing in control and AOC groups, partial healing in the ORC group and minimal healing in the MFC group. Fractional bone volume was 8 fold greater in the control and AOC groups than in the MFC group (0.42 ± 0.06, 0.40 ± 0.03 vs 0.05 ± 0.01, P < 0.001) and over 1.5-fold greater than in the ORC group (0.25 ± 0.03, P < 0.05). By histology, MFC remained at the application site with minimal healing at the defect margins and early fibrotic tissue within the defect. ORC-treated defects showed partial healing but with early fibrotic tissue in the marrow space. Conversely, control and AOC-treated defects demonstrated newly formed woven bone rich in cellular activity with no evidence of AOC remaining at the application site.
Early healing appeared to be impaired by the presence of MFC and impeded by the presence of ORC. In contrast, AOC did not inhibit bone healing and suggest that AOC may be a better bone hemostatic material for procedures where bony fusion is critical and immediate hemostasis required.
BMC Surgery 01/2010; 10:37. · 1.33 Impact Factor
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ABSTRACT: We previously reported that specific oxysterols stimulate osteogenic differentiation of pluripotent bone marrow stromal cells (MSCs) through activation of hedgehog (Hh) signaling and may serve as potential future therapies for intervention in osteopenia and osteoporosis. In this study we report that the osteogenic oxysterol 20(S)-hydroxycholesterol (20S) induces the expression of genes associated with Notch signaling. Using M2-10B4 (M2) MSCs, we found that 20S significantly induced HES-1, HEY-1, and HEY-2 mRNA expression compared with untreated cells, with maximal induction after 48 hours, whereas the nonosteogenic oxysterols did not. Similar observations were made when M2 cells were treated with sonic hedgehog (Shh), and the specific Hh pathway inhibitor cyclopamine blocked 20S-induced Notch target gene expression. 20S did not induce Notch target genes in Smo(-/-) mouse embryonic fibroblasts, further confirming the role of Hh signaling in 20S-induced expression of Notch target genes. Despite the inability of liver X-receptor (LXR) synthetic ligand TO901317 to induce Notch target genes in M2 cells, LXR knockdown studies using siRNA showed inhibition of 20S-induced HEY-1 but not HES-1 expression, suggesting the partial role of LXR signaling in MSC responses to 20S. Moreover, 20S-induced Notch target gene expression was independent of canonical Notch signaling because neither 20S nor Shh induced CBF1 luciferase reporter activity or NICD protein accumulation in the nucleus, which are hallmarks of canonical Notch signaling activation. Finally, HES-1 and HEY-1 siRNA transfection significantly inhibited 20S-induced osteogenic genes, suggesting that the pro-osteogenic effects of 20S are regulated in part by HES-1 and HEY-1.
Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 10/2009; 25(4):782-95. · 6.04 Impact Factor
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ABSTRACT: Hedgehog (Hh) signaling is indispensable in embryonic development, and its dysregulated activity results in severe developmental disorders as shown by genetic models of naturally occurring mutations in animal and human pathologies. Hh signaling also functions in postembryonic development and adult tissue homeostasis, and its aberrant activity causes various human cancers. Better understanding of molecular regulators of Hh signaling is of fundamental importance in finding new strategies for pathway modulation. Here, we identify liver X receptors (LXRs), members of the nuclear hormone receptor family, as previously unrecognized negative regulators of Hh signaling. Activation of LXR by specific pharmacological ligands, TO901317 and GW3965, inhibited the responses of pluripotent bone marrow stromal cells and calvaria organ cultures to sonic Hh, resulting in the inhibition of expression of Hh-target genes, Gli1 and Patched1, and Gli-dependent transcriptional activity. Moreover, LXR ligands inhibited sonic Hh-induced differentiation of bone marrow stromal cells into osteoblasts. Elimination of LXRs by small interfering RNA inhibited ligand-induced inhibition of Hh target gene expression. Furthermore, LXR ligand did not inhibit Hh responsiveness in mouse embryonic fibroblasts that do not express LXRs, whereas introduction of LXR into these cells reestablished the inhibitory effects. Daily oral administration of TO901317 to mice after 3 d significantly inhibited baseline Hh target-gene expression in liver, lung, and spleen. Given the importance of modulating Hh signaling in various physiological and pathological settings, our findings suggest that pharmacological targeting of LXRs may be a novel strategy for Hh pathway modulation.
Molecular Endocrinology 08/2009; 23(10):1532-43. · 4.54 Impact Factor
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ABSTRACT: The inflammatory cytokine interleukin-1 (IL-1) decreases mineralisation by immortalized mouse-derived cementoblastic cells (OC-CM cells), whilst various prostanoids, including fluprostenol (flup) increase it. Subtraction hybridisation conducted on flup minus IL-1-treated OC-CM cells revealed that one of the primary response genes preferentially induced by flup is the transcription factor Nur77. The objective of this study was to examine the signal transduction cascades regulating prostanoid induction of Nur77 gene expression in OC-CM cells.
Confluent OC-CM cells were treated with prostaglandin E(2) (PGE(2)), prostaglandin F(2alpha) (PGF(2alpha)), specific activators of the various EP prostanoid receptors and of the FP prostanoid receptor, and direct activators/inhibitors of the cyclic AMP-protein kinase A (PKA), protein kinase C (PKC) and intracellular calcium pathways. Nur77 gene expression was examined by mRNA extraction and Northern blot analysis.
PGE(2) and PGF(2alpha) treatment of OC-CM cells significantly increased Nur77 mRNA expression in a time- and dose-dependent fashion. Both the EP1 prostanoid receptor-specific activator 16,16-dimethyl-PGE(2) and the FP prostanoid receptor-specific activator flup significantly increased Nur77 gene expression by OC-CM cells as compared to vehicle-treated controls. Increase in Nur77 gene expression was also observed when direct activators of the PKA, PKC and intracellular calcium pathways were used to treat OC-CM cells. Direct inhibition of the PKA, PKC and intracellular calcium pathways abrogated Nur77 gene expression induced by OC-CM cell treatment with PGE(2) and PGF(2alpha).
Nur77 is a primary gene expressed by OC-CM cells and its induction appears to be mediated by the PKA, PKC and intracellular calcium pathways. Nur77 may affect expression of downstream target genes in OC-CM cells and partially regulate cementoblast cell function.
Archives of oral biology 03/2009; 54(5):412-9. · 1.65 Impact Factor
