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The flavonoid quercetin induces apoptosis and inhibits migration through a MAPK-dependent mechanism in osteoblasts
Tae Wook Nam1, Chong Il Yoo, Hui Taek Kim
1Department of Orthopedic Surgery, Pusan National University, Pusan, Korea.
Abstract:
The present study was undertaken to evaluate effects of quercetin, a major dietary flavonoid occurring in foods of plant origin, on cell viability and migration of osteoblastic cells. Quercetin inhibited cell viability, which was largely attributed to apoptosis, in a dose-and time-dependent manner in osteoblastic cells. Similar cytotoxicity of quercetin was observed in adipose tissue-derived stromal cells. Quercetin exerted a protective effect against H(2)O(2)-induced cell death, whereas it increased TNF-alpha-induced cell death. Western blot analysis showed that quercetin induced activation of ERK and p38, but not JNK. Quercetin-induced cell death was prevented by the ERK inhibitor PD98059, but not by inhibitors of p38 and JNK. Quercetin increased Bax expression and caused depolarization of mitochondrial membrane potential, which were inhibited by PD98059. Quercetin induced caspase-3 activation, and the quercetininduced cell death was prevented by caspase inhibitors. Quercetin inhibited cell migration, and its effect was prevented by inhibitors of ERK and p38. Taken together, these findings suggest that quercetin induces apoptosis through a mitochondria-dependent mechanism involving ERK activation and inhibits migration through activation of ERK and p38 pathways. Quercetin may exert both protective and deleterious effects in bone repair.
Insights
Quercetin, a dietary flavonoid, induces apoptosis in osteoblastic cells via mitochondrial pathways involving ERK activation. It also inhibits cell migration through ERK and p38 activation, suggesting complex roles in bone repair.
Area of Science:
- Biochemistry
- Cell Biology
- Pharmacology
Background:
- Quercetin is a prominent dietary flavonoid found in plant-based foods.
- Flavonoids are known for their diverse biological activities.
- Osteoblastic cells are crucial for bone formation and maintenance.
Purpose of the Study:
- To investigate the effects of quercetin on osteoblastic cell viability and migration.
- To elucidate the molecular mechanisms underlying quercetin's actions on these cells.
Main Methods:
- Osteoblastic cells and adipose tissue-derived stromal cells were treated with quercetin.
- Cell viability assays, apoptosis markers (Bax, caspase-3), mitochondrial membrane potential, and Western blot analysis were performed.
- Specific inhibitors for ERK, p38, and JNK pathways were used.
- Cell migration assays were conducted.
Main Results:
- Quercetin inhibited osteoblastic cell viability and induced apoptosis in a dose- and time-dependent manner.
- Quercetin protected against H(2)O(2)-induced cell death but increased TNF-alpha-induced cell death.
- Apoptosis involved mitochondrial pathway activation (Bax, mitochondrial membrane potential) and caspase-3 activation, mediated by ERK.
- Quercetin inhibited cell migration via ERK and p38 pathway activation.
Conclusions:
- Quercetin induces apoptosis in osteoblastic cells through a mitochondria-dependent mechanism involving ERK activation.
- Quercetin inhibits osteoblastic cell migration by activating ERK and p38 pathways.
- Quercetin exhibits dual effects, potentially protective and detrimental, in bone repair processes.
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