Effects of Cytokines on Alkaline Phosphatase and Osteocalcin Production, Calcification and Calcium Release by Human Osteoblastic Cells

Kuroki, Tetsuo; Sato, Masao; Kinoshita, Yasuko; Nobunaga, Masashi

doi:10.1093/rheumatology/33.3.224

Cited by 64 publications

(43 citation statements)

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“…IL-1b, TNF-a, and IFN-g have been shown to inhibit bone nodule formation, decrease ALP activity, inhibit OCN and col-I deposition, in both mouse and human osteoblasts [33,35,[59][60][61][62][63][64][65][66]. Many of these effects are mediated by NO and PGE 2 pathways, which are stimulated by these cytokines [32,67].…”

Section: Discussionmentioning

confidence: 99%

Comparison of Osteogenic Differentiation of Embryonic Stem Cells and Primary Osteoblasts Revealed by Responses to IL-1β, TNF-α, and IFN-γ

Sidney

Kirkham

Buttery

2014

Stem Cells and Development

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There are well-established approaches for osteogenic differentiation of embryonic stem cells (ESCs), but few show direct comparison with primary osteoblasts or demonstrate differences in response to external factors. Here, we show comparative analysis of in vitro osteogenic differentiation of mouse ESC (osteo-mESC) and mouse primary osteoblasts. Both cell types formed mineralized bone nodules and produced osteogenic extracellular matrix, based on immunostaining for osteopontin and osteocalcin. However, there were marked differences in the morphology of osteo-mESCs and levels of mRNA expression for osteogenic genes. In response to the addition of proinflammatory cytokines interleukin-1b, tumor necrosis factor-a, and interferon-g to the culture medium, primary osteoblasts showed increased production of nitric oxide (NO) and prostaglandin E 2 (PGE 2 ) at early time points and decreases in cell viability. In contrast, osteo-mESCs maintained viability and did not produce NO and PGE 2 until day 21. The formation of bone nodules by primary osteoblasts was reduced markedly after cytokine stimulation but was unaffected in osteo-mESCs. Cell sorting of osteo-mESCs by cadherin-11 (cad-11) showed clear osteogenesis of cad-11+ cells compared to unsorted osteo-mESCs and cad-11 -cells. Moreover, the cad-11 + cells showed a significant response to cytokines, similar to primary osteoblasts. Overall, these results show that while osteo-mESC cultures, without specific cell sorting, show characteristics of osteoblasts, there are also marked differences, notably in their responses to cytokine stimuli. These findings are relevant to understanding the differentiation of stem cells and especially developing in vitro models of disease, testing new drugs, and developing cell therapies.

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Section: Discussionmentioning

confidence: 99%

Comparison of Osteogenic Differentiation of Embryonic Stem Cells and Primary Osteoblasts Revealed by Responses to IL-1β, TNF-α, and IFN-γ

Sidney

Kirkham

Buttery

2014

Stem Cells and Development

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“…ALP is an important early marker of osteoblast differentiation (Kim et al 2004, ten Dijke et al 2003 which controls the precipitation of hydroxyapatite crystals in the early phase of mineralization in bone formation process (Anderson 2003, Manolagas 2000. Moreover, Chaudhary et al (2004) have reported that the ALP activity is closely associated with the formation of mineralized matrix while OCN, BGN and COL1A2 are major proteins commonly found in extracellular bone matrix and are believed to play an important role in bone formation (Chen et al 2003, 2004, Kuroki et al 1994, Parisuthiman et al 2005, Pischon et al 2004, Regazzoni et al 2001, Sierra et al 2003, Takeuchi et al 1996, Takuwa et al 1991, Viereck et al 2002, Young et al 2002.…”

Section: Discussionmentioning

confidence: 99%

Highly osteogenic PDL stem cell clones specifically express elevated levels of ICAM1, ITGB1 and TERT

Sununliganon

Singhatanadgit

2011

Cytotechnology

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Cells derived from the periodontal ligament (PDL) have previously been reported to have stem cell-like characteristics (PDL stem cells; PDLSCs) and play an important part in bone engineering, including that of alveolar bone. However, these populations have been heterogeneous, and thus far no specific marker has yet been established from adult human stem cells derived from PDL tissue. We have previously isolated highly purified single cellderived PDLSC clones and delineated their phenotypic and functional characteristics. In this report, we further obtained three homogeneous and distinct PDLSC clones demonstrating low, moderate and high mineralized matrix forming ability-namely PC12, PC4 and PC3, respectively, and the expression of mesenchymal stem cell pathway-specific genes in these clones was investigated. PCR array revealed that the expression of intercellular adhesion molecule 1 (ICAM1), integrin beta 1 (ITGB1) and telomerase reverse transcriptase (TERT) was associated with highly osteogenic PDLSC clones, as determined by the expression of key osteoblastic markers and their ability to form alizarin red S positive mineralized matrix in vitro. The present results suggest that these three mesenchymal stem cell-associated markers could potentially be used to isolate PDLSCs with high osteogenic capability for engineering new bone.

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“…22,23,28,[72][73][74][75][76][77][78] Although osteoblast differentiation is important in the evaluation of bone collagen, no studies in animal models or humans with renal failure have been reported. Our results showed a decrease in Runx2, Alpl, and Spp1 mRNA expression, despite increased osteoblast number in the adenine group, and a AGEs suppress LOX in the ROD rat C Aoki et al decrease in Spp1 mRNA in AGE-BSA-treated osteoblasts.…”

Section: Discussionmentioning

confidence: 99%

Advanced glycation end products suppress lysyl oxidase and induce bone collagen degradation in a rat model of renal osteodystrophy

Aoki

Uto

Honda

et al. 2013

Laboratory Investigation

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Renal osteodystrophy (ROD) is a major problem in patients with renal insufficiency. The present study was designed to elucidate the role of bone collagen changes and osteoblast differentiation in a rat model of ROD pathogenesis induced by adenine. Typical characteristics of renal failure, including increased serum urea nitrogen, creatinine, inorganic phosphorus, and intact parathyroid hormone levels, and decreased serum calcium and 1,25(OH) 2 D 3 levels, were observed in adenine-induced rats. Micro-computed tomography analysis of the femur in adenine-induced rats showed decreased bone mineral density and osteoporotic changes, confirmed by the three-point bending test. The cancellous bone histomorphometric parameters of the tibia showed increased osteoblast number, decreased osteoclast surface with peritrabecular fibrosis, and increased osteoid tissue, indicating a severe mineralization disorder similar to clinical ROD. Scanning and transmission electron microscopy revealed irregular alignment and increased diameter of bone collagen fibrils in adenine-induced rats. Protein expression analysis showed greater accumulation of advanced glycation end products (AGEs) in peritrabecular osteoblasts of adenine-induced rats than in the controls. In contrast, suppressed expression of runt-related transcription factor 2, alkaline phosphatase, secreted phosphoprotein 1 (Spp1), and lysyl oxidase (Lox) mRNA levels, particularly the amount of active LOX protein, were observed. In in-vitro experiments, mineralizing MC3T3-E1 osteoblastic cells stimulated with AGE-modified bovine serum albumin had attenuated the expression of Spp1 mRNA levels and active LOX protein, with a decrease in extracellular nodules of mineralization. These observations provide clues to ROD pathogenesis, as they indicate that the suppression of osteoblast differentiation and decreased active LOX protein associated with accumulation of AGEs in osteoblasts caused structural abnormalities of bone collagen fibrils and a severe mineralization disorder, leading to bone fragility.

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Effects of Cytokines on Alkaline Phosphatase and Osteocalcin Production, Calcification and Calcium Release by Human Osteoblastic Cells

Cited by 64 publications

References 0 publications

Comparison of Osteogenic Differentiation of Embryonic Stem Cells and Primary Osteoblasts Revealed by Responses to IL-1β, TNF-α, and IFN-γ

Comparison of Osteogenic Differentiation of Embryonic Stem Cells and Primary Osteoblasts Revealed by Responses to IL-1β, TNF-α, and IFN-γ

Highly osteogenic PDL stem cell clones specifically express elevated levels of ICAM1, ITGB1 and TERT

Advanced glycation end products suppress lysyl oxidase and induce bone collagen degradation in a rat model of renal osteodystrophy

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