Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10415 (Bcl-2)
 33,771 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bone degradation is a serious complication of chronic inflammatory diseases such as septic arthritis, osteomyelitis, and infected orthopedic implant failure. Up to date, effective therapeutic treatments for bacteria-caused bone destruction are limited. In our previous study, we found that LPS promoted osteoclast differentiation and activity through activation of mitogen-activated protein kinases (MAPKs) pathway such as c-Jun N-terminal kinases (JNK) and extracellular signal regulated kinase (ERK1/2). The current study was to evaluate the mechanism of LPS on the apoptosis and osteoblast differentiation in MC3T3-E1 cells. MC3T3-E1 osteoblasts were non-treated, treated with LPS. After treatment, the cell viability, the activity of alkaline phosphatase (ALP) and caspase-3 were measured. The expressions of osteoblast-specific genes and Bax, Bcl-2, and caspase-3 were determined by real-time quantitative polymerase chain reaction (qPCR). Protein levels of Bax, Bcl-2, caspase-3, and phosphorylation of MAPKs were measured using Western blotting assays. The MAPK signaling pathway was blocked by pretreatment with JNK inhibitor SP600125. LPS treatment induced a significant decrease in cell metabolism, viability, and ALP activity in MC3T3-E1 cells. LPS also significantly decreased mRNA expressions of osteoblast-related genes in MC3T3-E1 cells. On the other hand, LPS significantly upregulated mRNA expressions and protein levels of Bax and caspase-3 as well as activation of caspase-3, whereas decreased Bcl-2 expression in MC3T3-E1 cells. Furthermore, LPS significantly promoted MAPK pathway including the phosphorylation of JNK and the phosphorylation of ERK1/2; moreover, pretreatment with JNK inhibitor not only attenuated both of phosphorylation-JNK and ERK1/2 enhanced by LPS in MC3T3-E1 cells, but also reversed the downregulated expressions of osteoblast-specific genes including ALP and BSP induced by LPS. In conclusion, LPS could induce osteoblast apoptosis and inhibit osteoblast differentiation via activation of JNK pathway.
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PMID:Lipopolysaccharide (LPS) induces the apoptosis and inhibits osteoblast differentiation through JNK pathway in MC3T3-E1 cells. 2427 71

Bone degradation is a serious complication of chronic inflammatory diseases such as septic arthritis, osteomyelitis, and infected orthopedic implant failure. Effective therapeutic treatments for bacteria-caused bone destruction are limited. In a previous study, we found that lipopolysaccharide (LPS) induced osteoblast apoptosis and inhibited early and late-stage differentiation of osteoblasts via activation of the C-Jun N-terminal kinase (JNK) pathway. This study aimed to investigate the effect of JNK inhibition by SP600125 on the apoptosis and differentiation of MC3T3-E1 osteoblasts suppressed by LPS. Following pretreatment with SP600125 for 2 h, MC3T3-E1 cells were treated LPS. Following this treatment, cell viability, activity of alkaline phosphatase (ALP) and caspase-3 were measured. mRNA and protein expression of osteoblast-specific genes, mitogen-activated protein kinases (MAPKs), Bax, Bcl-2 and caspase-3 were determined by quantitative polymerase chain reaction (qPCR) and western blot analysis. The results showed that SP600125 significantly restored LPS-inhibited cell metabolism and ALP activity and reduced the upregulated caspase-3 activity of MC3T3-E1 cells induced by LPS. SP600125 also significantly restored the LPS-suppressed mRNA and protein expression levels of early-stage osteoblast-associated genes in a dose-dependent manner. SP600125 significantly downregulated expression of Bax and caspase-3 but upregulated Bcl-2 expression in MC3T3-E1 cells stimulated by LPS. Furthermore, SP600125 selectively triggered the MAPK pathway by reducing the expression of JNK1, while enhancing the expression of extracellular signal-regulated kinase 1 (ERK1). Our results suggested that SP600125 reduced LPS-induced osteoblast apoptosis and restored early-stage differentiation of osteoblasts inhibited by LPS through MAPK signaling. These findings suggest that the therapeutic agent that inhibited JNK1 is of potential use for the restoration of osteoblast function in bacteria-induced bone diseases.
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PMID:SP600125 reduces lipopolysaccharide-induced apoptosis and restores the early-stage differentiation of osteoblasts inhibited by LPS through the MAPK pathway in MC3T3-E1 cells. 2576 15

Chronic osteomyelitis, a bone infectious disease, is characterized by dysregulation of bone homeostasis, which results in excessive bone resorption. Lipopolysaccharide (LPS) which is a gram-negative endotoxin was shown to inhibit osteoblast differentiation and to induce apoptosis and osteoclasts formation in vitro. While effective therapy against bacteria-induced bone destruction is quite limited, the investigation of potential drugs that restore down-regulated osteoblast function remains a major goal in the prevention of bone destruction in infective bone diseases. This investigation aimed to rescue LPS-induced MC3T3-E1 pre-osteoblastic cell line using the methanolic extract of Cladophora glomerata enriched with Mn(II) ions by biosorption. LPS-induced MC3T3-E1 cultures supplemented with C. glomerata methanolic extract were tested for expression of the main genes and microRNAs involved in the osteogenesis pathway using RT-PCR. Moreover, osteoclastogenesis of 4B12 cells was also investigated by tartrate-resistant acid phosphatase (TRAP) assay. Treatment with algal extract significantly restored LPS-suppressed bone mineralization and the mRNA expression levels of osteoblast-specific genes such as runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP) and osteocalcin (OCN), osteopontin (OPN), miR-27a and miR-29b. The extract also inhibited osteoblast apoptosis, significantly restored the down-regulated expression of Bcl-2, and decreased the loss of MMP and reactive oxygen spices (ROS) production in MC3T3-E1 cells induced by LPS. Furthermore, pre-treatment with algal extract strongly decreased the activation of osteoclast in MC3T3-E1-4B12 coculture system stimulated by LPS. Our findings suggest that C. glomerata enriched with Mn(II) ions may be a potential raw material for the development of drug for preventing abnormal bone loss induced by LPS in bacteria-induced bone osteomyelitis.
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PMID:Cladophora glomerata enriched by biosorption with Mn(II) ions alleviates lipopolysaccharide-induced osteomyelitis-like model in MC3T3-E1, and 4B12 osteoclastogenesis. 3249 6