GRIP1 enhances estrogen receptor α-dependent extracellular matrix gene expression in chondrogenic cells

SummaryObjectiveThe role of postmenopause on the pathogenesis of cartilage degeneration has been an open question. We assessed cartilage degeneration in estrogen receptor (ER)α null mice and examined the role of glucocorticoid receptor-interacting protein 1 (GRIP1) in the ERα-dependent transcription of a type II collagen gene (col2a1) with special reference to a crosstalk with the transforming growth factor (TGF)-β signaling pathway.MethodsThe vertebral cartilaginous endplate from female ERα null mice was subjected to histological analyses. Col2a1 expression of primary chondrocytes (PCs) obtained from ERα null mice after 17β-estradiol (E2) and TGF-β1 stimulation was examined by reverse transcription polymerase chain reaction (RT-PCR). Estrogen response element (ERE) or col2a1 promoter–enhancer luciferase reporter system was used to investigate the crosstalk among ERα, GRIP1, and MKK6. Col2a1 expression and glycosaminoglycan (GAG) content were measured in ATDC5 cells treated with GRIP1 small interfering RNA (siRNA).ResultsERα deficiency clearly accelerated impairment of the vertebral cartilaginous endplate. E2 and TGF-β1 stimulation increased col2a1 expression in PC from wild-type mice, but not that from ERα null mice. The same stimulation increased the col2a1 promoter–enhancer reporter activity, and the elevated activity was decreased by dominant-negative ERα and p38 mitogen-activated protein kinase (MAPK) inhibitor. GRIP1 increased the E2-dependent ERE activation in the presence of ERα and constitutive-active MKK6. GRIP1 siRNA repressed col2a1 expression and GAG production in ATDC5 cells.ConclusionsCrosstalks between ERα/GRIP1 and TGF-β/MKK6/p38 MAPK pathway have protective roles on cartilage metabolism via regulating the extracellular matrices expression. The finding may lead to the development of a novel therapeutic approach for cartilage degeneration

Application of CR-39 plastic nuclear track detectors for quality assurance of mixed oxide fuel pellets

A CR-39 plastic nuclear track detector was used for quality assurance of mixed oxide fuel pellets for next-generation nuclear power plants. Plutonium (Pu) spot sizes and concentrations in the pellets are significant parameters for safe use in the plants. We developed an automatic Pu detection system based on dense α-radiation tracks in the CR-39 detectors. This system would greatly improve image processing time and measurement accuracy, and will be a powerful tool for rapid pellet quality assurance screening