Wnt/β-catenin signaling is critical for various cellular processes in multiple cell types,including osteoblast(OB)differentiation and function.Exactly how Wnt/β-catenin signaling is regulated in OBs remain elusive.A...Wnt/β-catenin signaling is critical for various cellular processes in multiple cell types,including osteoblast(OB)differentiation and function.Exactly how Wnt/β-catenin signaling is regulated in OBs remain elusive.ATP6AP2,an accessory subunit of V-ATPase,plays important roles in multiple cell types/organs and multiple signaling pathways.However,little is known whether and how ATP6AP2 in OBs regulates Wnt/β-catenin signaling and bone formation.Here we provide evidence for ATP6AP2 in the OB-lineage cells to promote OB-mediated bone formation and bone homeostasis selectively in the trabecular bone regions.Conditionally knocking out(CKO)ATP6AP2 in the OB-lineage cells(Atp6ap2^(Ocn-Cre))reduced trabecular,but not cortical,bone formation and bone mass.Proteomic and cellular biochemical studies revealed that LRP6 and N-cadherin were reduced in ATP6AP2-KO BMSCs and OBs,but not osteocytes.Additional in vitro and in vivo studies revealed impairedβ-catenin signaling in ATP6AP2-KO BMSCs and OBs,but not osteocytes,under both basal and Wnt stimulated conditions,although LRP5 was decreased in ATP6AP2-KO osteocytes,but not BMSCs.Further cell biological studies uncovered that osteoblastic ATP6AP2 is not required for Wnt3a suppression ofβ-catenin phosphorylation,but necessary for LRP6/β-catenin and N-cadherin/β-catenin protein complex distribution at the cell membrane,thus preventing their degradation.Expression of activeβ-catenin diminished the OB differentiation deficit in ATP6AP2-KO BMSCs.Taken together,these results support the view for ATP6AP2 as a critical regulator of both LRP6 and N-cadherin protein trafficking and stability,and thus regulatingβ-catenin levels,demonstrating an un-recognized function of osteoblastic ATP6AP2 in promoting Wnt/LRP6/β-catenin signaling and trabecular bone formation.展开更多
Liliangyou 3822 is a novel indica hybrid rice variety that exhibits disease resistance,high yield,lodging resistance,and late maturity.It employs a self-selected two-line sterile line,Li 38S,and a self-selected restor...Liliangyou 3822 is a novel indica hybrid rice variety that exhibits disease resistance,high yield,lodging resistance,and late maturity.It employs a self-selected two-line sterile line,Li 38S,and a self-selected restorer line,R22.This variety was subjected to a regional test of indica late-maturing groups in the middle and lower reaches of the Yangtze River in 2020.The results demonstrated that the average yield of the variety was 9.95 t/hm 2,which was 10.67%higher than that of the control Fengliangyou 4,indicating a highly significant yield increase.In the continuous test in 2021,the average yield was 9.74 t/hm 2,representing a 6.52%increase over the control,which also exhibited a significant increase.Finally,the average yield of the two years regional test was 9.84 t/hm 2,which was 8.58%higher than that of the control.In the 2021 production test,the average yield of the variety was 9.32 t/hm 2,which was 12.19%higher than that of the control,indicating a remarkably significant yield increase.In 2022,the variety was validated by the National Crop Variety Approval Committee(GSD 20220143).展开更多
基金supported in part by grants from the National Institutes of Health(AG045781,AG051510,and AG066526)(to WCX).
文摘Wnt/β-catenin signaling is critical for various cellular processes in multiple cell types,including osteoblast(OB)differentiation and function.Exactly how Wnt/β-catenin signaling is regulated in OBs remain elusive.ATP6AP2,an accessory subunit of V-ATPase,plays important roles in multiple cell types/organs and multiple signaling pathways.However,little is known whether and how ATP6AP2 in OBs regulates Wnt/β-catenin signaling and bone formation.Here we provide evidence for ATP6AP2 in the OB-lineage cells to promote OB-mediated bone formation and bone homeostasis selectively in the trabecular bone regions.Conditionally knocking out(CKO)ATP6AP2 in the OB-lineage cells(Atp6ap2^(Ocn-Cre))reduced trabecular,but not cortical,bone formation and bone mass.Proteomic and cellular biochemical studies revealed that LRP6 and N-cadherin were reduced in ATP6AP2-KO BMSCs and OBs,but not osteocytes.Additional in vitro and in vivo studies revealed impairedβ-catenin signaling in ATP6AP2-KO BMSCs and OBs,but not osteocytes,under both basal and Wnt stimulated conditions,although LRP5 was decreased in ATP6AP2-KO osteocytes,but not BMSCs.Further cell biological studies uncovered that osteoblastic ATP6AP2 is not required for Wnt3a suppression ofβ-catenin phosphorylation,but necessary for LRP6/β-catenin and N-cadherin/β-catenin protein complex distribution at the cell membrane,thus preventing their degradation.Expression of activeβ-catenin diminished the OB differentiation deficit in ATP6AP2-KO BMSCs.Taken together,these results support the view for ATP6AP2 as a critical regulator of both LRP6 and N-cadherin protein trafficking and stability,and thus regulatingβ-catenin levels,demonstrating an un-recognized function of osteoblastic ATP6AP2 in promoting Wnt/LRP6/β-catenin signaling and trabecular bone formation.
文摘Liliangyou 3822 is a novel indica hybrid rice variety that exhibits disease resistance,high yield,lodging resistance,and late maturity.It employs a self-selected two-line sterile line,Li 38S,and a self-selected restorer line,R22.This variety was subjected to a regional test of indica late-maturing groups in the middle and lower reaches of the Yangtze River in 2020.The results demonstrated that the average yield of the variety was 9.95 t/hm 2,which was 10.67%higher than that of the control Fengliangyou 4,indicating a highly significant yield increase.In the continuous test in 2021,the average yield was 9.74 t/hm 2,representing a 6.52%increase over the control,which also exhibited a significant increase.Finally,the average yield of the two years regional test was 9.84 t/hm 2,which was 8.58%higher than that of the control.In the 2021 production test,the average yield of the variety was 9.32 t/hm 2,which was 12.19%higher than that of the control,indicating a remarkably significant yield increase.In 2022,the variety was validated by the National Crop Variety Approval Committee(GSD 20220143).
