In the synovial joint,mechanical force creates an important signal that influences chondrocyte behavior.The conversion of mechanical signals into biochemical cues relies on different elements in mechanotransduction pa...In the synovial joint,mechanical force creates an important signal that influences chondrocyte behavior.The conversion of mechanical signals into biochemical cues relies on different elements in mechanotransduction pathways and culminates in changes in chondrocyte phenotype and extracellular matrix composition/structure.Recently,several mechanosensors,the first responders to mechanical force,have been discovered.However,we still have limited knowledge about the downstream molecules that enact alterations in the gene expression profile during mechanotransduction signaling.Recently,estrogen receptorα(ERα)has been shown to modulate the chondrocyte response to mechanical loading through a ligand-independent mechanism,in line with previous research showing that ERαexerts important mechanotransduction effects on other cell types,such as osteoblasts.In consideration of these recent discoveries,the goal of this review is to position ERαinto the mechanotransduction pathways known to date.Specifically,we first summarize our most recent understanding of the mechanotransduction pathways in chondrocytes on the basis of three categories of actors,namely mechanosensors,mechanotransducers,and mechanoimpactors.Then,the specific roles played by ERαin mediating the chondrocyte response to mechanical loading are discussed,and the potential interactions of ERαwith other molecules in mechanotransduction pathways are explored.Finally,we propose several future research directions that may advance our understanding of the roles played by ERαin mediating biomechanical cues under physiological and pathological conditions.展开更多
基金supported by the Department of Orthopaedic Surgery at the University of Pittsburghthe Department of Orthopaedic Surgery at Xiangya Hospital,Central South Universitypartially supported by the Pennsylvania Department of Health。
文摘In the synovial joint,mechanical force creates an important signal that influences chondrocyte behavior.The conversion of mechanical signals into biochemical cues relies on different elements in mechanotransduction pathways and culminates in changes in chondrocyte phenotype and extracellular matrix composition/structure.Recently,several mechanosensors,the first responders to mechanical force,have been discovered.However,we still have limited knowledge about the downstream molecules that enact alterations in the gene expression profile during mechanotransduction signaling.Recently,estrogen receptorα(ERα)has been shown to modulate the chondrocyte response to mechanical loading through a ligand-independent mechanism,in line with previous research showing that ERαexerts important mechanotransduction effects on other cell types,such as osteoblasts.In consideration of these recent discoveries,the goal of this review is to position ERαinto the mechanotransduction pathways known to date.Specifically,we first summarize our most recent understanding of the mechanotransduction pathways in chondrocytes on the basis of three categories of actors,namely mechanosensors,mechanotransducers,and mechanoimpactors.Then,the specific roles played by ERαin mediating the chondrocyte response to mechanical loading are discussed,and the potential interactions of ERαwith other molecules in mechanotransduction pathways are explored.Finally,we propose several future research directions that may advance our understanding of the roles played by ERαin mediating biomechanical cues under physiological and pathological conditions.
