Cytotoxic effect of bone cements in HL-60 cells: Distinction between apoptosis and necrosis

Ciapetti, G.; Granchi, Donatella; Cenni, E.; Savarino, L.; Cavedagna, D.; Pizzoferrato, Alberto

doi:10.1002/1097-4636(200011)52:2<338::aid-jbm13>3.0.co;2-l

Cited by 50 publications

(18 citation statements)

References 21 publications

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“…Pain-sensitive nerve endings seem to be damaged by the extensive impact of heat, and therefore local pain seems to be reduced additionally [36]. Polymerization of bone cement results in a partly severe cytotoxicity [38][39][40]. However, toxic effects due to PMMA in bone are not clearly understood yet.…”

Section: Evaluation Of Painmentioning

confidence: 99%

Percutaneous vertebroplasty in the therapy of osteoporotic vertebral compression fractures: a critical review

et al. 2006

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Percutaneous vertebroplasty has become an efficient technique for the treatment of painful vertebral fractures. Osteoporotic vertebral compression fractures are characterized by severe back pain and immobilization causing other complications like thrombosis or pneumonia. Vertebral cement augmentation provides increased strength of the vertebral body and an obvious pain relief. Between 1989 and 2004, 30 studies and a total of 2,086 treated patients have been published in literature. A review of these studies has been performed. The number and age of the patients, number of treated vertebrae, pre- and postoperative outcome of pain and complications of the different studies were assessed and analyzed. Percutaneous vertebroplasty is an efficient technique with low complication rates and a significant reduction in pain. It rapidly improves the mobility and quality of life of patients with vertebral compression fractures. With an increasing number of treated patients, experience with this interventional technique has become excellent. But still there are no randomized controlled trials available, showing that percutaneous vertebroplasty has a significantly better outcome than other treatment options, especially after a long-term follow-up.

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Section: Evaluation Of Painmentioning

confidence: 99%

Percutaneous vertebroplasty in the therapy of osteoporotic vertebral compression fractures: a critical review

et al. 2006

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“…On the contrary in our samples the presence of cement increased the percentage of TdT positive cells. In fact bone cements have been shown to induce in vitro apoptosis in osteoblast-like and HL-60 cells [11,12]. These observations suggest that the apoptosis observed in the cementless samples could be mainly a ''physiological'' apoptosis occurring during the normal tissue turnover [5].…”

Section: Discussionmentioning

confidence: 99%

Fibroblast apoptosis and caspase-8 activation in aseptic loosening

et al. 2003

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“…Studies by Pioletti et al, 1 Wang et al, 2 and MacQuarrie et al 3 have shown that titanium particles induce apoptosis in rat calvarial osteoblasts, human mesenchymal stem cells, and murine osteoclasts, while studies by MacQuarrie et al, 3 Horowitz et al, 4 De Guzman et al, 5 and Ciapetti et al 6 have shown that PMMA particles induce cell necrosis in osteoclasts, macrophages, fibroblasts, and HL-60 leukemic cells. Our study corroborates these findings and suggest that necrosis, rather than apoptosis, was observed in MC3T3-E1 osteoprogenitor cultures challenged with PMMA particles.…”

Section: Discussionmentioning

confidence: 99%

“…We hypothesize that the inhibition of osteoprogenitor differentiation by PMMA particles results from impairment of cell viability and direct inhibition of transcription factors that promote osteogenesis. Given that PMMA particles cause cell necrosis, not apoptosis, in osteoclasts, macrophages, and fibroblasts, [3][4][5][6] we hypothesize that PMMA particles also induce osteoprogenitor cell death by a necrotic, rather than an apoptotic, mechanism. In this study, we examined the effects of PMMA particles on the viability of MC3T3-E1 osteoprogenitor cells and their expression of Runx2, osterix, Dlx5, Msx2, and b-catenin during osteogenic differentiation.…”

mentioning

confidence: 89%

“…Studies have shown that titanium particles cause apoptosis of rat calvarial osteoblasts 1 and human mesenchymal stem cells, 2 and that polymethylmethacrylate (PMMA) particles cause necrosis of osteoclasts, 3 macrophages, 4 fibroblasts, 5 and HL-60 leukemic cells. 6 Titanium particles have also been shown to inhibit matrix mineralization of osteoblasts 7,8 and osteogenic differentiation of human mesenchymal stem cells. 9,10 Given that osteoprogenitors are the precursors to osteoblasts, the survival and differentiation of these cells is crucial to the process of bone formation in the implant bed during exposure to wear particles.…”

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confidence: 99%

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Polymethylmethacrylate particles impair osteoprogenitor viability and expression of osteogenic transcription factors Runx2, osterix, and Dlx5

Chiu¹,

Smith²,

Gene³

et al. 2009

Journal Orthopaedic Research

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Polymethylmethacrylate (PMMA) particles have been shown to inhibit the differentiation of osteoprogenitor cells, but the mechanism of this inhibitory effect has not been investigated. We hypothesize that the inhibitory effects of PMMA particles involve impairment of osteoprogenitor viability and direct inhibition of transcription factors that regulate osteogenesis. We challenged MC3T3-E1 osteoprogenitors with PMMA particles and examined the effects of these materials on osteoprogenitor viability and expression of transcription factors Runx2, osterix, Dlx5, and Msx2. MC3T3-E1 cells treated with PMMA particles over a 72-h period showed a significant reduction in cell viability and proliferation as indicated by a dose-and time-dependent increase in supernatant levels of lactate dehydrogenase, an intracellular enzyme released from dead cells, a dose-dependent decrease in cell number and BrdU uptake, and the presence of large numbers of positively labeled Annexin V-stained cells. The absence of apoptotic cells on TUNEL assay indicated that cell death occurred by necrosis, not apoptosis. MC3T3-E1 cells challenged with PMMA particles during the first 6 days of differentiation in osteogenic medium showed a significant dose-dependent decrease in the RNA expression of Runx2, osterix, and Dlx5 on all days of measurement, while the RNA expression of Msx2, an antagonist of Dlx5-induced osteogenesis, remained relatively unaffected. These results indicate that PMMA particles impair osteoprogenitor viability and inhibit the expression of transcription factors that promote osteoprogenitor differentiation. 7,8 and osteogenic differentiation of human mesenchymal stem cells. 9,10 Given that osteoprogenitors are the precursors to osteoblasts, the survival and differentiation of these cells is crucial to the process of bone formation in the implant bed during exposure to wear particles.Osteoprogenitor differentiation is regulated by the transcription factors Runx2, osterix, Dlx5, and Msx2, and the transcriptional activator b-catenin. 11 Runx2 dictates the expression of key osteoblast proteins such as alkaline phosphatase, collagen, and osteocalcin, and is expressed in bone cells throughout the osteogenic lineage. 11 Osterix lies downstream of Runx2 and is required for the differentiation of pre-osteoblasts into mature osteoblasts. 11,12 Dlx5 is a homeobox domain transcription factor that also regulates osteogenesis [13][14][15] and is involved in the response of osteogenic cells to BMP-2. [16][17][18] Msx2, another homeodomain transcription factor, is a functional antagonist and repressor of Dlx5-induced osteogenesis. 19-23 b-Catenin, a transcriptional activator of the canonical Wnt signaling pathway, associates with the DNA-binding proteins TCF and LEF, and stimulates Runx2 transcription. 11,24,25 Expression of these transcription factors is normally required for the proper differentiation of osteoprogenitor cells.Our group has previously shown that PMMA particles inhibit the osteogenic differentiation of murine MC3T3-E1 ...

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Cytotoxic effect of bone cements in HL-60 cells: Distinction between apoptosis and necrosis

Cited by 50 publications

References 21 publications

Percutaneous vertebroplasty in the therapy of osteoporotic vertebral compression fractures: a critical review

Percutaneous vertebroplasty in the therapy of osteoporotic vertebral compression fractures: a critical review

Fibroblast apoptosis and caspase-8 activation in aseptic loosening

Polymethylmethacrylate particles impair osteoprogenitor viability and expression of osteogenic transcription factors Runx2, osterix, and Dlx5

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