Effect of Risedronate on Osteoblast Differentiation, Expression of Receptor Activator of NF‐κB Ligand and Apoptosis in Mesenchymal Stem Cells
: Nitrogen‐containing bisphosphonates (BPs) are antiresorptive drugs used for the treatment of metabolic bone diseases. Bone marrow stromal cells such as mesenchymal stem cells (MSCs) and MSC‐derived osteoblasts that originate from MSCs are known to regulate osteoclast differentiation and activatio...
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| Veröffentlicht in: | Basic & clinical pharmacology & toxicology 2011-08, Vol.109 (2), p.78-84 |
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| creator | Fujita, Hirofumi Kurokawa, Kazuko Ogino, Tetsuya Ono, Mio Yamamoto, Masanao Oka, Takashi Nakanishi, Tohru Kobayashi, Naoya Tanaka, Noriaki Ogawa, Tomohiro Suzaki, Etsuko Utsumi, Kozo Sasaki, Junzo |
| description | : Nitrogen‐containing bisphosphonates (BPs) are antiresorptive drugs used for the treatment of metabolic bone diseases. Bone marrow stromal cells such as mesenchymal stem cells (MSCs) and MSC‐derived osteoblasts that originate from MSCs are known to regulate osteoclast differentiation and activation via the expression of receptor activator of NF‐κB ligand (RANKL). Although the effects of nitrogen‐containing BPs on osteoclasts and osteoblasts have been well investigated, their effects in MSCs have not been clarified. In this study, we investigated the effects of risedronate (RIS), a nitrogen‐containing BP, on osteoblast differentiation, RANKL expression and apoptosis in human and rat MSCs. RIS suppressed the formation of mineralized nodules and mRNA expression of differentiation marker genes such as bone sialoprotein and osteocalcin in MSC‐derived osteoblasts. The RANKL expression induced by 1,25‐(OH)2 vitamin D3 was not affected by RIS in human MSC‐derived osteoblasts. In addition, treatment with high‐concentration RIS induced chromatin condensation, an apoptosis feature, in MSCs. RIS‐induced chromatin condensation was suppressed by a pan‐caspase inhibitor zVAD‐FMK and a cell‐permeable isoprenoid analogue geranylgeraniol. These results indicate that RIS suppressed osteoblast differentiation and induced caspase‐ and isoprenoid depletion‐dependent apoptosis and suggest that the antiresorptive effect of RIS is not mediated by a decrease in the RANKL expression in MSC‐derived osteoblasts. |
| doi_str_mv | 10.1111/j.1742-7843.2011.00685.x |
| format | Article |
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Bone marrow stromal cells such as mesenchymal stem cells (MSCs) and MSC‐derived osteoblasts that originate from MSCs are known to regulate osteoclast differentiation and activation via the expression of receptor activator of NF‐κB ligand (RANKL). Although the effects of nitrogen‐containing BPs on osteoclasts and osteoblasts have been well investigated, their effects in MSCs have not been clarified. In this study, we investigated the effects of risedronate (RIS), a nitrogen‐containing BP, on osteoblast differentiation, RANKL expression and apoptosis in human and rat MSCs. RIS suppressed the formation of mineralized nodules and mRNA expression of differentiation marker genes such as bone sialoprotein and osteocalcin in MSC‐derived osteoblasts. The RANKL expression induced by 1,25‐(OH)2 vitamin D3 was not affected by RIS in human MSC‐derived osteoblasts. In addition, treatment with high‐concentration RIS induced chromatin condensation, an apoptosis feature, in MSCs. RIS‐induced chromatin condensation was suppressed by a pan‐caspase inhibitor zVAD‐FMK and a cell‐permeable isoprenoid analogue geranylgeraniol. These results indicate that RIS suppressed osteoblast differentiation and induced caspase‐ and isoprenoid depletion‐dependent apoptosis and suggest that the antiresorptive effect of RIS is not mediated by a decrease in the RANKL expression in MSC‐derived osteoblasts.</description><identifier>ISSN: 1742-7835</identifier><identifier>EISSN: 1742-7843</identifier><identifier>DOI: 10.1111/j.1742-7843.2011.00685.x</identifier><identifier>PMID: 21332944</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Animals ; Apoptosis - drug effects ; Biological and medical sciences ; Bone Density Conservation Agents - pharmacology ; Cell Differentiation - drug effects ; Cells, Cultured ; Etidronic Acid - analogs & derivatives ; Etidronic Acid - pharmacology ; Humans ; Medical sciences ; Mesenchymal Stromal Cells - cytology ; Mesenchymal Stromal Cells - drug effects ; Osteoblasts - cytology ; Osteoblasts - drug effects ; Pharmacology. 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Bone marrow stromal cells such as mesenchymal stem cells (MSCs) and MSC‐derived osteoblasts that originate from MSCs are known to regulate osteoclast differentiation and activation via the expression of receptor activator of NF‐κB ligand (RANKL). Although the effects of nitrogen‐containing BPs on osteoclasts and osteoblasts have been well investigated, their effects in MSCs have not been clarified. In this study, we investigated the effects of risedronate (RIS), a nitrogen‐containing BP, on osteoblast differentiation, RANKL expression and apoptosis in human and rat MSCs. RIS suppressed the formation of mineralized nodules and mRNA expression of differentiation marker genes such as bone sialoprotein and osteocalcin in MSC‐derived osteoblasts. The RANKL expression induced by 1,25‐(OH)2 vitamin D3 was not affected by RIS in human MSC‐derived osteoblasts. In addition, treatment with high‐concentration RIS induced chromatin condensation, an apoptosis feature, in MSCs. RIS‐induced chromatin condensation was suppressed by a pan‐caspase inhibitor zVAD‐FMK and a cell‐permeable isoprenoid analogue geranylgeraniol. These results indicate that RIS suppressed osteoblast differentiation and induced caspase‐ and isoprenoid depletion‐dependent apoptosis and suggest that the antiresorptive effect of RIS is not mediated by a decrease in the RANKL expression in MSC‐derived osteoblasts.</description><subject>Animals</subject><subject>Apoptosis - drug effects</subject><subject>Biological and medical sciences</subject><subject>Bone Density Conservation Agents - pharmacology</subject><subject>Cell Differentiation - drug effects</subject><subject>Cells, Cultured</subject><subject>Etidronic Acid - analogs & derivatives</subject><subject>Etidronic Acid - pharmacology</subject><subject>Humans</subject><subject>Medical sciences</subject><subject>Mesenchymal Stromal Cells - cytology</subject><subject>Mesenchymal Stromal Cells - drug effects</subject><subject>Osteoblasts - cytology</subject><subject>Osteoblasts - drug effects</subject><subject>Pharmacology. 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Bone marrow stromal cells such as mesenchymal stem cells (MSCs) and MSC‐derived osteoblasts that originate from MSCs are known to regulate osteoclast differentiation and activation via the expression of receptor activator of NF‐κB ligand (RANKL). Although the effects of nitrogen‐containing BPs on osteoclasts and osteoblasts have been well investigated, their effects in MSCs have not been clarified. In this study, we investigated the effects of risedronate (RIS), a nitrogen‐containing BP, on osteoblast differentiation, RANKL expression and apoptosis in human and rat MSCs. RIS suppressed the formation of mineralized nodules and mRNA expression of differentiation marker genes such as bone sialoprotein and osteocalcin in MSC‐derived osteoblasts. The RANKL expression induced by 1,25‐(OH)2 vitamin D3 was not affected by RIS in human MSC‐derived osteoblasts. In addition, treatment with high‐concentration RIS induced chromatin condensation, an apoptosis feature, in MSCs. RIS‐induced chromatin condensation was suppressed by a pan‐caspase inhibitor zVAD‐FMK and a cell‐permeable isoprenoid analogue geranylgeraniol. These results indicate that RIS suppressed osteoblast differentiation and induced caspase‐ and isoprenoid depletion‐dependent apoptosis and suggest that the antiresorptive effect of RIS is not mediated by a decrease in the RANKL expression in MSC‐derived osteoblasts.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>21332944</pmid><doi>10.1111/j.1742-7843.2011.00685.x</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Apoptosis - drug effects Biological and medical sciences Bone Density Conservation Agents - pharmacology Cell Differentiation - drug effects Cells, Cultured Etidronic Acid - analogs & derivatives Etidronic Acid - pharmacology Humans Medical sciences Mesenchymal Stromal Cells - cytology Mesenchymal Stromal Cells - drug effects Osteoblasts - cytology Osteoblasts - drug effects Pharmacology. Drug treatments RANK Ligand - analysis Rats Risedronate Sodium |
| title | Effect of Risedronate on Osteoblast Differentiation, Expression of Receptor Activator of NF‐κB Ligand and Apoptosis in Mesenchymal Stem Cells |
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