Genistein improves bone healing via triggering estrogen receptor alpha-mediated expressions of osteogenesis-associated genes and consequent maturation of osteoblasts
Journal
Journal of Agricultural and Food Chemistry
Journal Volume
68
Journal Issue
39
Pages
10639-10650
Date Issued
2020
Author(s)
Abstract
Osteoporosis-associated fractures may cause higher morbidity and mortality. Our previous study showed the effects of genistein, a phytoestrogen, on the induction of estrogen receptor alpha (ERα) gene expression and stimulation of osteoblast mineralization. In this study, rat calvarial osteoblasts and an animal bone defect model were used to investigate the effects of genistein on bone healing. Treatment with genistein caused a time-dependent increase in alkaline phosphatase (ALP) activity in rat osteoblasts. Levels of cytosolic and nuclear ERα significantly augmented following exposure to genistein. Subsequently, genistein elevated levels of ALP mRNA and protein in rat osteoblasts. Moreover, genistein induced other osteogenesis-associated osteocalcin and Runx2 mRNA and protein expressions. Knocking-down ERα using RNA interference concurrently inhibited genistein-induced Runx2, osteocalcin, and ALP mRNA expression. Attractively, administration of ICR mice suffering bone defects with genistein caused significant increases in the callus width, chondrocyte proliferation, and ALP synthesis. Results of microcomputed tomography revealed that administration of genistein increased trabecular bone numbers and improved the bone thickness and volume. This study showed that genistein can improve bone healing via triggering ERα-mediated osteogenesis-associated gene expressions and subsequent osteoblast maturation. ? 2020 American Chemical Society
Subjects
Alkaline phosphatase; Bone healing; Genistein; Osteoblast maturation; Osteogenesis-associated gene
SDGs
Other Subjects
Computerized tomography; Defects; Diseases; Flavonoids; Gene expression; Phosphatases; Rats; Alkaline phosphatase activity; Chondrocyte proliferation; Estrogen receptor; Microcomputed tomography; Osteoblast maturation; Osteoblast mineralization; Protein expressions; RNA interference; Bone; alkaline phosphatase; estrogen receptor alpha; genistein; osteocalcin; phytoestrogen; transcription factor RUNX2; animal; bone; bone development; bone regeneration; cytology; drug effect; female; genetics; human; Institute for Cancer Research mouse; metabolism; mouse; osteoblast; osteoporosis; pathophysiology; rat; Alkaline Phosphatase; Animals; Bone and Bones; Bone Regeneration; Core Binding Factor Alpha 1 Subunit; Estrogen Receptor alpha; Female; Genistein; Humans; Mice; Mice, Inbred ICR; Osteoblasts; Osteocalcin; Osteogenesis; Osteoporosis; Phytoestrogens; Rats
Publisher
American Chemical Society
Type
journal article