Peri-implant keratinized mucosa(PIKM)augmentation refers to surgical procedures aimed at increasing the width of PIKM.Consensus reports emphasize the necessity of maintaining a minimum width of PIKM to ensure long-ter...Peri-implant keratinized mucosa(PIKM)augmentation refers to surgical procedures aimed at increasing the width of PIKM.Consensus reports emphasize the necessity of maintaining a minimum width of PIKM to ensure long-term peri-implant health.Currently,several surgical techniques have been validated for their effectiveness in increasing PIKM.However,the selection and application of PIKM augmentation methods may present challenges for dental practitioners due to heterogeneity in surgical techniques,variations in clinical scenarios,and anatomical differences.Therefore,clear guidelines and considerations for PIKM augmentation are needed.This expert consensus focuses on the commonly employed surgical techniques for PIKM augmentation and the factors influencing their selection at second-stage surgery.It aims to establish a standardized framework for assessing,planning,and executing PIKM augmentation procedures,with the goal of offering evidence-based guidance to enhance the predictability and success of PIKM augmentation.展开更多
The axon guidance cue SLIT3 was identified as an osteoanabolic agent in two recent reports. However, these reports conflict in their nomination of osteoblasts versus osteoclasts as the key producers of skeletal SLIT3 ...The axon guidance cue SLIT3 was identified as an osteoanabolic agent in two recent reports. However, these reports conflict in their nomination of osteoblasts versus osteoclasts as the key producers of skeletal SLIT3 and additionally offer conflicting data on the effects of SLIT3 on osteoclastogenesis. Here, aiming to address this discrepancy, we found no observable SLIT3 expression during human or mouse osteoclastogenesis and the only modest SLIT3-mediated effects on osteoclast differentiation. Conditional deletion of SLIT3 in cathepsin K(CTSK)-positive cells, including osteoclasts, had no effect on the number of osteoclast progenitors, in vitro osteoclast differentiation, overall bone mass, or bone resorption/formation parameters. Similar results were observed with the deletion of SLIT3 in Lys M-positive cells, including osteoclast lineage cells. Consistent with this finding, bone marrow chimeras made from Slit3-/-donors that lacked SLIT3 expression at all stages of osteoclast development displayed normal bone mass relative to controls. Taken in context, multiple lines of evidence were unable to identify the physiologic function of osteoclast-derived SLIT3,indicating that osteoblasts are the major source of skeletal SLIT3.展开更多
Development of alternatively activated （M2） macrophage phenotypes is a complex process that is coordinately regulated by a plethora of pathways and factors. Here, we report that RBP-J, a DNA-binding protein that int...Development of alternatively activated （M2） macrophage phenotypes is a complex process that is coordinately regulated by a plethora of pathways and factors. Here, we report that RBP-J, a DNA-binding protein that integrates signals from multiple pathways including the Notch pathway, is critically involved in polarization of M2 macrophages. Mice deficient in RBP-J in the myeloid compartment exhibited impaired M2 phenotypes in vivo in a chitin-induced model of M2 polarization. Consistent with the in vivo findings, M2 polarization was partially compromised in vitro in Rbpj-deficient macrophages as demonstrated by reduced expression of a subset of M2 effector molecules including arginase 1. Functionally, myeloid Rbpj deficiency impaired M2 effector functions including recruitment of eosinophils and suppression of T cell proliferation. Collectively, we have identified RBP- Jas an essential regulator of differentiation and function of alternatively activated macrophages.展开更多
MicroRNAs(miRNAs)have been widely implicated in immune regulation,but evidence for the coordinated function of paralogous miRNA clusters remains scarce.Here,by using genetically modified mice with individual or combin...MicroRNAs(miRNAs)have been widely implicated in immune regulation,but evidence for the coordinated function of paralogous miRNA clusters remains scarce.Here,by using genetically modified mice with individual or combined cluster deficiencies,we found that three paralogous clusters of the miR-17-92 family of miRNAs collectively suppressed IL-12 production in macrophages.Accordingly,miR-17-92 family miRNAs deficiencies resulted in heightened production of IL-12 and thus enhanced the host defense against intracellular pathogen Listeria monocytogenes in vivo.Mechanistically,different members of the miR-17-92 family of miRNAs acted on a common target,PTEN,to inhibit IL-12 expression by modulating the PI3K-Akt-GSK3 pathway.In addition,the expression of miR-17-92 family miRNAs was collectively inhibited by the transcription factor RBP-J,and RBP-J-associated macrophage functional defects were genetically rescued by deleting three clusters of miR-17-92 family miRNAs on a RBP-J null background.Thus,our results illustrated key roles of three clusters of miR-17-92 family miRNAs in cooperatively controlling IL-12-mediated immune responses and identified miR-17-92 family miRNAs as functional targets of RBP-J in macrophages.展开更多
Pattern-recognition receptors,such as toll-like receptors(TLRs),detect a wide range of microbial products and initiate innate immune responses leading to the production of inflammatory mediators.In addition,TLR signal...Pattern-recognition receptors,such as toll-like receptors(TLRs),detect a wide range of microbial products and initiate innate immune responses leading to the production of inflammatory mediators.In addition,TLR signaling also activates expression of Notch target genes that play crucial roles in suppression of TLR-triggered inflammatory responses.However,whether TLR signaling pathways engaged by other classes of pattern-recognition receptors induce expression of Notch target genes remains unclear.Here we demonstrate that zymosan,a stimulus for TLR2 and dectin-1,strongly induces expression of multiple Notch target genes in both human and murine dendritic cells.Mechanistically,induction of Notch targets by zymosan is both TLR2-and Syk-dependent through activation of mitogen-activated protein kinases and the transcription factor c-Fos.Hence,our data reveals a novel mechanism that efficient induction of Notch target genes requires engagement of TLR and dectin-1/Syk signaling pathways.展开更多
基金supported by the Natural Science Foundation of Sichuan Province(grant number:25NSFSC0265).
文摘Peri-implant keratinized mucosa(PIKM)augmentation refers to surgical procedures aimed at increasing the width of PIKM.Consensus reports emphasize the necessity of maintaining a minimum width of PIKM to ensure long-term peri-implant health.Currently,several surgical techniques have been validated for their effectiveness in increasing PIKM.However,the selection and application of PIKM augmentation methods may present challenges for dental practitioners due to heterogeneity in surgical techniques,variations in clinical scenarios,and anatomical differences.Therefore,clear guidelines and considerations for PIKM augmentation are needed.This expert consensus focuses on the commonly employed surgical techniques for PIKM augmentation and the factors influencing their selection at second-stage surgery.It aims to establish a standardized framework for assessing,planning,and executing PIKM augmentation procedures,with the goal of offering evidence-based guidance to enhance the predictability and success of PIKM augmentation.
基金an Award Program for the Minjiang Scholar Professorship in Fujian Province, a start-up grant from Xiamen University and support from the National Natural Science Foundation of China (81972034 to RX)supported by the NIH grant DP5OD021351supported by NIH grants (R01AR068970, AR071463)。
文摘The axon guidance cue SLIT3 was identified as an osteoanabolic agent in two recent reports. However, these reports conflict in their nomination of osteoblasts versus osteoclasts as the key producers of skeletal SLIT3 and additionally offer conflicting data on the effects of SLIT3 on osteoclastogenesis. Here, aiming to address this discrepancy, we found no observable SLIT3 expression during human or mouse osteoclastogenesis and the only modest SLIT3-mediated effects on osteoclast differentiation. Conditional deletion of SLIT3 in cathepsin K(CTSK)-positive cells, including osteoclasts, had no effect on the number of osteoclast progenitors, in vitro osteoclast differentiation, overall bone mass, or bone resorption/formation parameters. Similar results were observed with the deletion of SLIT3 in Lys M-positive cells, including osteoclast lineage cells. Consistent with this finding, bone marrow chimeras made from Slit3-/-donors that lacked SLIT3 expression at all stages of osteoclast development displayed normal bone mass relative to controls. Taken in context, multiple lines of evidence were unable to identify the physiologic function of osteoclast-derived SLIT3,indicating that osteoblasts are the major source of skeletal SLIT3.
基金We thank Tasuko Honjo for providing Rbpj^flox/flox mice, Keiko Ozato for providing Ifr8^-/- mice, and Karmen Au for technical assistance. LBI and BZ are supported by the grants from NIH. XH is supported by the National Basic Research Program （973 Program） （No. 2015CB943201）, National Natural Science Foundation of China Young Investigator Award 81422019, and funds from Peking-Tsin- ghua Center of Life Sciences.
文摘Development of alternatively activated （M2） macrophage phenotypes is a complex process that is coordinately regulated by a plethora of pathways and factors. Here, we report that RBP-J, a DNA-binding protein that integrates signals from multiple pathways including the Notch pathway, is critically involved in polarization of M2 macrophages. Mice deficient in RBP-J in the myeloid compartment exhibited impaired M2 phenotypes in vivo in a chitin-induced model of M2 polarization. Consistent with the in vivo findings, M2 polarization was partially compromised in vitro in Rbpj-deficient macrophages as demonstrated by reduced expression of a subset of M2 effector molecules including arginase 1. Functionally, myeloid Rbpj deficiency impaired M2 effector functions including recruitment of eosinophils and suppression of T cell proliferation. Collectively, we have identified RBP- Jas an essential regulator of differentiation and function of alternatively activated macrophages.
基金supported by the Ministry of Science and Technology of China National Key Research Projects(2015CB943201 to X.H.and 2015CB943200 to L.W.)National Natural Science Foundation of China grants(31821003,31725010,81571580,91642115,and 81661130161 to X.H.and 31330027 to LW.)+2 种基金funds from Tsinghua-Peking Center for Life Sciences(X.H.,L.W.,and XZ)funds from the Institute for Immunology at Tsinghua University(X.H.and L.W.)funds from the National Institutes of Health(BZ).
文摘MicroRNAs(miRNAs)have been widely implicated in immune regulation,but evidence for the coordinated function of paralogous miRNA clusters remains scarce.Here,by using genetically modified mice with individual or combined cluster deficiencies,we found that three paralogous clusters of the miR-17-92 family of miRNAs collectively suppressed IL-12 production in macrophages.Accordingly,miR-17-92 family miRNAs deficiencies resulted in heightened production of IL-12 and thus enhanced the host defense against intracellular pathogen Listeria monocytogenes in vivo.Mechanistically,different members of the miR-17-92 family of miRNAs acted on a common target,PTEN,to inhibit IL-12 expression by modulating the PI3K-Akt-GSK3 pathway.In addition,the expression of miR-17-92 family miRNAs was collectively inhibited by the transcription factor RBP-J,and RBP-J-associated macrophage functional defects were genetically rescued by deleting three clusters of miR-17-92 family miRNAs on a RBP-J null background.Thus,our results illustrated key roles of three clusters of miR-17-92 family miRNAs in cooperatively controlling IL-12-mediated immune responses and identified miR-17-92 family miRNAs as functional targets of RBP-J in macrophages.
基金supported by grants from the National Natural Science Foundation of China 31725010 and 31821003(XH),grant from the Shandong Provincial Natural Science Foundation,China ZR2017MC021(YS)funds from the Tsinghua-Peking Center for Life Sciences and Institute for Immunology at Tsinghua University(XH),funds from the Peak Discipline Construction Plan of Shandong Province and Shandong Agricultural University(YS),and grants from the NIH(BZ).
文摘Pattern-recognition receptors,such as toll-like receptors(TLRs),detect a wide range of microbial products and initiate innate immune responses leading to the production of inflammatory mediators.In addition,TLR signaling also activates expression of Notch target genes that play crucial roles in suppression of TLR-triggered inflammatory responses.However,whether TLR signaling pathways engaged by other classes of pattern-recognition receptors induce expression of Notch target genes remains unclear.Here we demonstrate that zymosan,a stimulus for TLR2 and dectin-1,strongly induces expression of multiple Notch target genes in both human and murine dendritic cells.Mechanistically,induction of Notch targets by zymosan is both TLR2-and Syk-dependent through activation of mitogen-activated protein kinases and the transcription factor c-Fos.Hence,our data reveals a novel mechanism that efficient induction of Notch target genes requires engagement of TLR and dectin-1/Syk signaling pathways.
