S100A4 inhibition by RNAi up-regulates osteoblast related genes in periodontal ligament cells

Kato, Chizuru; Kojima, Toshihiko; Komaki, Motohiro; Mimori, Kaori; Duarte, Wagner R.; Takenaga, Keizo; Ishikawa, Isao

doi:10.1016/j.bbrc.2004.11.010

Cited by 45 publications

(33 citation statements)

References 36 publications

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“…As in the case of some other genes, such as lamin A/C in HeLa SS6 cells (27) and S100A4 in periodontal ligament cells (28), the Mapkapk2 siRNA knocked down the basal Mapkapk2 expression almost completely. It also repressed the OGP-(10 -14) stimulation of Mapkapk2 mRNA (Fig.…”

Section: Mapkapk2 Mediates the Mitogenic Effect Of Ogp-(10 -14)-mentioning

confidence: 69%

ERK1/2-activated de Novo Mapkapk2 Synthesis Is Essential for Osteogenic Growth Peptide Mitogenic Signaling in Osteoblastic Cells

Miguel

Namdar-Attar

Noh

et al. 2005

Journal of Biological Chemistry

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In osteoblasts, the mitogen-activated protein kinases ERK1/2 and p38 as well as the cAMP-response element-binding protein (CREB) have been implicated in the regulation of proliferation and differentiation. The osteogenic growth peptide (OGP) is a 14-mer bone cell mitogen that increases bone formation and trabecular bone density and stimulates fracture healing. OGP-(10 -14) is the physiologically active form of OGP. Using gene array analysis, real-time reverse transcription-PCR, and immunoblot and DNA synthesis assays we show here that in MC3T3 E1 and newborn mouse calvarial osteoblastic cultures the OGP-(10 -14) mitogenic signaling is critically dependent on de novo synthesis of mitogen-activated protein kinase-activated protein kinase 2 (Mapkapk2) mRNA and protein.The increase in Mapkapk2 occurs following short term (5-60 min) stimulation of ERK1/2 activity by OGP-(10 -14); phosphorylation of p38 remains unaffected. Downstream of Mapkapk2, CREB is phosphorylated on Ser 133 leading to its enhanced transcriptional activity. That these events are critical for the OGP-(10 -14) mitogenic signaling is demonstrated by blocking the effects of OGP-(10 -14) on the ERK1/2 pathway, Mapkapk2, CREB, and DNA synthesis using the MEK inhibitor PD098059. The OGP-(10 -14) stimulation of CREB transcriptional activity and DNA synthesis is also blocked by Mapkapk2 siRNA. These data define a novel mitogenic signaling pathway in osteoblasts whereby ERK1/2 stimulation of CREB phosphorylation and transcriptional activity as well as DNA synthesis are critically dependent on de novo Mapkapk2 synthesis.In mammalian cells, the family of mitogen-activated protein (MAP) 3 kinases provides a key link between membrane-bound receptors and changes in the pattern of gene expression. The MAP kinases are activated downstream of many different types of receptors, including tyrosine kinase receptors, cytokine receptors, and serpentine G-protein coupled receptors (1, 2). The MAP kinases consist of four subfamilies: the extracellular signal-regulated kinases 1 and 2 (ERK1/2), c-Jun N-terminal kinase/stress-activated kinase, p38 MAP kinase, and ERK 5. Further downstream, they regulate a multitude of transcription factors that control cell proliferation, survival, and differentiation (3, 4). In osteoblasts, ERK1/2-dependent phosphorylation cascades have been implicated in the regulation of proliferation and RUNX2 activity (5, 6). Activation of p38 has been demonstrated in osteoblasts undergoing differentiation after stimulation with bone morphogenetic protein-2 and epidermal growth factor (7,8).The osteogenic growth peptide (OGP) is a 14-mer bone cell mitogen that increases bone formation and trabecular bone density and stimulates fracture healing when administered to mice and rats (9 -11). Transgenic mice overexpressing OGP have a markedly increased peak bone mass (12). OGP is present in mammalian serum in micromolar concentrations mainly complexed to ␣ 2 -macroglobulin (13). Upon its dissociation from the complex, it is proteolytically activated yieldin...

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Section: Mapkapk2 Mediates the Mitogenic Effect Of Ogp-(10 -14)-mentioning

confidence: 69%

ERK1/2-activated de Novo Mapkapk2 Synthesis Is Essential for Osteogenic Growth Peptide Mitogenic Signaling in Osteoblastic Cells

Miguel

Namdar-Attar

Noh

et al. 2005

Journal of Biological Chemistry

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“…Colony-forming efficiency was 15-25% at passage 1 (data not shown). RT-PCR revealed that these cells expressed known PDL-specific markers of S100A4 [19,20] and periostin [21] (Fig. 1B).…”

Section: Resultsmentioning

confidence: 95%

“…PDL tissues are very unique because they are never calcified spontaneously even they are located in a close gap between two types of hard tissues, bone and cementum. Duarte et al proposed that S100A4 can be a negative regulator of mineralization in PDL tissues [19,20]. Periostin that is known to be strongly expressed in PDL tissues [21] is suggested to be essential for the integrity and function of PDL [22].…”

Section: Discussionmentioning

confidence: 97%

“…Despite intensive research efforts, no definitive markers specific to PDL cells have not been shown. Among these candidates reported previously, gene expression of S100A4 [19,20] and periostin [21] were examined and both genes were expressed by isolated PDL cells in the present study. PDL tissues are very unique because they are never calcified spontaneously even they are located in a close gap between two types of hard tissues, bone and cementum.…”

Section: Discussionmentioning

confidence: 99%

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Periodontal regeneration with multi-layered periodontal ligament-derived cell sheets in a canine model

et al. 2009

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“…S100A4 is expressed in normal tissues such as smooth muscle, liver, bone marrow, smooth muscle cell of arteries, kidney, and osteoblastic cells in rats and humans. However, the physiological functions of S100A4 in normal tissues have not been clarified yet (15,16). A specific functional activity of S100A4 has been reported in its colocalization with cytoskeletal proteins F-actin and non-muscle myosin (17)(18)(19)(20)(21)(22)(23)(24).…”

mentioning

confidence: 99%

Expression of the Calcium-binding Protein S100A4 Is Markedly Up-regulated by Osmotic Stress and Is Involved in the Renal Osmoadaptive Response

Rivard

Brown

Almeida

et al. 2007

Journal of Biological Chemistry

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Proteomic analysis of Inner Medullary Collecting Duct (IMCD3) cells adapted to increasing levels of tonicity (300, 600, and 900 mosmol/kg H 2 O) by two-dimensional difference gel electrophoresis and mass spectrometry revealed several proteins as yet unknown to be up-regulated in response to hypertonic stress. Of these proteins, one of the most robustly up-regulated (22-fold) was S100A4. The identity of the protein was verified by high pressure liquid chromatography-mass spectrometry. Western blot analysis confirmed increased expression with increased tonicity, both acute and chronic. S100A4 protein expression was further confirmed by immunocytochemical analysis. Cells grown in isotonic conditions showed complete absence of immunostaining, whereas chronically adapted IMCD3 cells had uniform cytoplasmic localization. The protein is also regulated in vivo as in mouse kidney tissues S100A4 expression was many -fold greater in the papilla as compared with the cortex and increased further in the papilla upon 36 h of thirsting. Increased expression of S100A4 was also observed in the medulla and papilla, but not the cortex of a human kidney. Data from Affymetrix gene chip analysis and quantitative PCR also revealed increased S100A4 message in IMCD3 cells adapted to hypertonicity. The initial expression of message increased at 8 -10 h following exposure to acute sublethal hypertonic stress (550 mosmol/kg H 2 O). Protein and message half-life in IMCD3 cells were 85.5 and 6.8 h, respectively. Increasing medium tonicity with NaCl, sucrose, mannitol, and choline chloride stimulated S100A4 expression, whereas urea did not. Silencing of S100A4 expression using a stable siRNA vector (pSM2; Open Biosystems) resulted in a 48-h delay in adaptation of IMCD3 cells under sublethal osmotic stress, suggesting S100A4 is involved in the osmoadaptive response. In summary, we describe the heretofore unrecognized up-regulation of a small calcium-binding protein, both in vitro and in vivo, whose absence profoundly delays osmoadaptation and slows cellular growth under hypertonic conditions.

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S100A4 inhibition by RNAi up-regulates osteoblast related genes in periodontal ligament cells

Cited by 45 publications

References 36 publications

ERK1/2-activated de Novo Mapkapk2 Synthesis Is Essential for Osteogenic Growth Peptide Mitogenic Signaling in Osteoblastic Cells

ERK1/2-activated de Novo Mapkapk2 Synthesis Is Essential for Osteogenic Growth Peptide Mitogenic Signaling in Osteoblastic Cells

Periodontal regeneration with multi-layered periodontal ligament-derived cell sheets in a canine model

Expression of the Calcium-binding Protein S100A4 Is Markedly Up-regulated by Osmotic Stress and Is Involved in the Renal Osmoadaptive Response

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