Studies of the Levamisole inhibitory effect on rat stromal‐cell commitment to mineralization

Klein, Benjamin Y.; Gal, I.; Segal, David

doi:10.1002/jcb.240530204

Cited by 27 publications

(10 citation statements)

References 22 publications

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“…Alp is another marker gene for bone cell maturation and mineralization. Inhibition of alp activation, by for example heat or by gene knockout, inhibits calcification and causes mineralization defects in cultured bone cells and mice [37]. In addition, mutations in the alp gene lead to hypophosphatasia, in which bone matrix formation occurs, but mineralization is inhibited [38].…”

Section: Discussionmentioning

confidence: 99%

Molecular pathology of vertebral deformities in hyperthermic Atlantic salmon (Salmo salar)

et al. 2010

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BackgroundHyperthermia has been shown in a number of organisms to induce developmental defects as a result of changes in cell proliferation, differentiation and gene expression. In spite of this, salmon aquaculture commonly uses high water temperature to speed up developmental rate in intensive production systems, resulting in an increased frequency of skeletal deformities. In order to study the molecular pathology of vertebral deformities, Atlantic salmon was subjected to hyperthermic conditions from fertilization until after the juvenile stage.ResultsFish exposed to the high temperature regime showed a markedly higher growth rate and a significant higher percentage of deformities in the spinal column than fish reared at low temperatures. By analyzing phenotypically normal spinal columns from the two temperature regimes, we found that the increased risk of developing vertebral deformities was linked to an altered gene transcription. In particular, down-regulation of extracellular matrix (ECM) genes such as col1a1, osteocalcin, osteonectin and decorin, indicated that maturation and mineralization of osteoblasts were restrained. Moreover, histological staining and in situ hybridization visualized areas with distorted chondrocytes and an increased population of hypertrophic cells. These findings were further confirmed by an up-regulation of mef2c and col10a, genes involved in chondrocyte hypertrophy.ConclusionThe presented data strongly indicates that temperature induced fast growth is severely affecting gene transcription in osteoblasts and chondrocytes; hence change in the vertebral tissue structure and composition. A disrupted bone and cartilage production was detected, which most likely is involved in the higher rate of deformities developed in the high intensive group. Our results are of basic interest for bone metabolism and contribute to the understanding of the mechanisms involved in development of temperature induced vertebral pathology. The findings may further conduce to future molecular tools for assessing fish welfare in practical farming.

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Section: Discussionmentioning

confidence: 99%

Molecular pathology of vertebral deformities in hyperthermic Atlantic salmon (Salmo salar)

et al. 2010

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“…ALP participates in the differentiation of osteoblasts and provides phosphate for hydroxyapatite mineral formation (36) . Inhibition of ALP inhibits differentiation and mineralization of osteoblast cultures, (37) and its impaired expression in hypophosphatasia in humans is associated with defects in bone mineralization (38) . Also necessary for proper differentiation and mineralization of osteoblasts is collagen I expression (29–31) .…”

Section: Discussionmentioning

confidence: 99%

Atherogenic Diet and Minimally Oxidized Low Density Lipoprotein Inhibit Osteogenic and Promote Adipogenic Differentiation of Marrow Stromal Cells

Parhami

Jackson

Tintut

et al. 1999

Journal of Bone and Mineral Research

237

178

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In osteoporosis, the bone marrow stroma osteogenic cell population declines and adipocyte numbers increase. We recently showed that oxidized lipids inhibit differentiation of preosteoblasts. In this report, we assess the effect of minimally oxidized low density lipoprotein (MM-LDL) on osteoblastic differentiation of murine marrow stromal cells, M2-10B4. MM-LDL, but not native LDL, inhibited stromal cell osteoblastic differentiation as demonstrated by inhibition of alkaline phosphatase activity, collagen I processing, and mineralization, through a mitogenactivated protein kinase-dependent pathway. In addition, marrow stromal cells from C57BL/6 mice fed a high fat, atherogenic diet failed to undergo osteogenic differentiation in vitro. The ability of MM-LDL to regulate adipogenesis was also assessed. Treatment of M2-10B4 as well as 3T3-L1 preadipocytes with MM-LDL, but not native LDL, promoted adipogenic differentiation in the presence of peroxisome proliferator-activated receptor (PPAR) ␥ agonist thiazolidinediones, BRL49653 and ciglitizone. Based on promoter-reporter construct experiments, MM-LDL may be acting in part through activating PPAR␣. These observations suggest that LDL oxidation products promote osteoporotic loss of bone by directing progenitor marrow stromal cells to undergo adipogenic instead of osteogenic differentiation. These data lend support to the "lipid hypothesis of osteoporosis." (J Bone Miner Res

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“…Alkaline Phosphatase Assay-Organophosphate hydrolytic activity on the surface of viable UMR cells was determined in the presence or absence of PTH-(1-34) via a modification of an existing in situ assay (34). Briefly, p-nitrophenyl phosphate (final concentration of 10 mM) was added to living cultures bathed in phenol red-free medium and placed in a rotary shaking incubator at 37°C.…”

Section: Methodsmentioning

confidence: 99%

Reversible Suppression of in Vitro Biomineralization by Activation of Protein Kinase A

Wang

Martin

Lembke

et al. 2000

Journal of Biological Chemistry

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Parathyroid hormone (PTH-(1-34)) potently suppresses apatite deposition in osteoblastic cultures. These inhibitory effects are mediated through signaling events following PTH receptor binding. Using both selective inhibitors and activators of protein kinase A (PKA), this study shows that a transient activation of PKA is sufficient to account for PTH's inhibition of apatite deposition. This inhibition is not a result of reduced cell proliferation, reduced alkaline phosphatase activity, increased collagenase production, or lowering medium pH. Rather, data suggest a functional relationship between matrix assembly and apatite deposition in vitro. Bone sialoprotein (BSP) and apatite co-localize in the extracellular matrix of mineralizing cultures, with matrix deposition of BSP temporally preceding that of apatite. Transient activation of PKA by either PTH-(1-34) or short term cAMP analog treatment blocks the deposition of BSP in the extracellular matrix without a significant reduction in the total amount of BSP synthesized and secreted. This effect is reversible after allowing the cultures to recover in the absence of PKA activators for several days. Thus, a transient activation of PKA may suppress mineral deposition in vitro as a consequence of altering the assembly of an extracellular matrix permissive for apatite formation.The need to better understand the biological nature of bone mineralization is illustrated by the fact that a properly mineralized endoskeleton is crucial for vertebrate survival (1, 2). To date, several biomineralization theories have been formulated, and each advances a mechanistic model to explain bone formation (3). Lately, these models have emphasized the role of several bone-specific, noncollagenous proteins (4) as promoting the tightly regulated processes of apatite crystal nucleation and growth in an extracellular environment. One such candidate is bone sialoprotein (BSP), 1 a sulfated, phosphorylated matrix glycoprotein (5-8) with a restricted pattern of expression within mineralizing tissues (9 -16), which co-localizes with the smallest detectable foci of newly forming mineralized matrix in osteoid (17).Parathyroid hormone (PTH) is a calciotropic hormone that can stimulate either formation or resorption of bone in vivo depending on such factors as dosage, delivery modality, and treatment frequency (18 -21). In vitro, a continuous exposure to PTH results in the suppression of biomineralization in primary cultures of calvarial osteoblasts (22), calvarial explants (23), or growth plate chondrocytes (24, 25). However, the molecular mechanisms mediating PTH's inhibitory effect on in vitro biomineralization reactions have not been elucidated yet. The first 34 amino acid residues in PTH contain most of the biological activity of the full-length, natural hormone including ligand-receptor binding and signal transduction functions (26, 27). Two major plasma membrane reactions occur as a result of PTH's binding to its receptor that then initiate three intracellular signaling cascades. First, there...

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Studies of the Levamisole inhibitory effect on rat stromal‐cell commitment to mineralization

Cited by 27 publications

References 22 publications

Molecular pathology of vertebral deformities in hyperthermic Atlantic salmon (Salmo salar)

Molecular pathology of vertebral deformities in hyperthermic Atlantic salmon (Salmo salar)

Atherogenic Diet and Minimally Oxidized Low Density Lipoprotein Inhibit Osteogenic and Promote Adipogenic Differentiation of Marrow Stromal Cells

Reversible Suppression of in Vitro Biomineralization by Activation of Protein Kinase A

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