Response of Gli1+ Suture Stem Cells to Mechanical Force Upon Suture Expansion

Normal development of craniofacial sutures is crucial for cranial and facial growth in all three dimensions. These sutures provide a unique niche for suture stem cells (SuSCs), which are indispensable for homeostasis, damage repair, as well as stress balance. Expansion appliances are now routinely used to treat underdevelopment of the skull and maxilla, stimulating the craniofacial sutures through distraction osteogenesis. However, various treatment challenges exist due to a lack of full understanding of the mechanism through which mechanical forces stimulate suture and bone remodeling. To address this issue, we first identified crucial steps in the cycle of suture and bone remodeling based on the established standard suture expansion model. Observed spatiotemporal morphological changes revealed that the remodeling cycle is approximately 3 to 4 weeks, with collagen restoration proceeding more rapidly. Next, we traced the fate of the Gli1⁺ SuSCs lineage upon application of tensile force in three dimensions. SuSCs were rapidly activated and greatly contributed to bone remodeling within 1 month. Furthermore, we confirmed the presence of Wnt activity within Gli1⁺ SuSCs based on the high co-expression ratio of Gli1⁺ cells and Axin2⁺ cells, which also indicated the homogeneity and heterogeneity of two cell groups. Because Wnt signaling in the sutures is highly upregulated upon tensile force loading, conditional knockout of β-catenin largely restricted the activation of Gli1⁺ SuSCs and suppressed bone remodeling under physiological and expansion conditions. Thus, we concluded that Gli1⁺ SuSCs play essential roles in suture and bone remodeling stimulated by mechanical force and that Wnt signaling is crucial to this process. © 2022 American Society for Bone and Mineral Research (ASBMR).     

HGF/SF in Mammary Epithelial Growth and Morphogenesis: In Vitro and In Vivo Models

HGF/SF is a multifunctional cytokine whichthrough binding to its cellular receptor, c-MET, canelicit mitogenic, morphogenic and motogenic responses intarget cells. Expression of HGF/SF and c-MET has been shown to be critical in earlyembryogenesis affecting development of many organs andtissues. The effects of HGF/SF4 on established human andmouse mammary cell lines have previously been reported. This review describes the source and targetsfor HGF/SF in both human and mouse mammary tissue anddiscusses the effects of HGF/SF on primary mouse andhuman mammary epithelial cells in vitro, detailing the individual response of the two epithelialsub-population of cells which comprise this organ.Additionally, the effects of HGF/SF overexpression onmouse mammary gland development in vivo, aresummarized.     

Mammary Epithelial Stem Cells: Our Current Understanding

It has recently been shown that the progeny froma single cell may comprise the epithelial population ofa fully developed lactating mammary outgrowth in mice.Serial transplantation of epithelial fragments from this clonally derived gland demonstratesthat the subsequently generated outgrowths are alsocomprised of progeny from the original antecedent.Similarly, genetic analysis of contiguous portions of individual human mammary ducts within the samebreast indicates their clonal derivation. Theseobservations support the concept that multipotenttissue-specific epithelial stem cells are present amongthe parenchymal cells of the mammary gland. Here,we present the developing evidence for the presence ofstem cells in virtually every renewing mammalian tissueas well as some classically considered to consist only of differentiated cells. Further, wereview the present morphologic and biologic evidence forstem cells and lineage-limited progenitor cells in humanand rodent mammary epithelium. Although a number of selective markers are known for variouslineage-limited hematopoietic cells and their progeny,our understanding of the biology of the precursor cellsfor mammary epithelium is just beginning. Our purpose here is to develop further interest in theclarification of these issues in the biology of themammary gland.     

中药对细胞因子和NK细胞活性的调节作用

综述了中药在调节细胞因子和免疫效应细胞活性方面的研究进展。大量临床观察和动物实验表明,中药可广泛调节白细胞介素(LK_s)、干扰素(IFN)等的生成和活性,可影响自然杀伤细胞(NK)等的细胞毒活性。在分子、细胞水平开展中药免疫调节机理的研究,有助于揭示中药对于机体整合的药理作用和与功能状态相关的调节效应。文章亦分析了中药免疫药理的量效关系,体内与体外研究的关系,中药与有效成分的关系。     

祛风凉血法对慢性特发性血小板减少性紫癜患者T细胞亚群及NK细胞的影响

【目的】探讨祛风凉血法在治疗慢性特发性血小板减少性紫癜（ITP）中的作用。【方法】将确诊为慢性血热妄行型ITP患者13例给予祛风凉血中药（主要由苍耳子、蝉蜕、防风、荆芥、水牛角、丹皮、仙鹤草、生地、侧柏叶、赤芍、三七末、甘草等组成）治疗,观察治疗前后ITP患者外周血T细胞亚群和自然杀伤细胞（NK细胞）的变化,并与正常对照组进行比较。【结果】治疗前患者外周血T细胞亚群CD3、CD4、CD4／CD8比值（PCD4/PCD8）和NK细胞水平均低于正常对照组,而CD8含量明显增多（P〈0．001）;经祛风凉血法治疗后,T淋巴细胞CD3、CD4、PCD4／PCD8和NK细胞均有不同程度的上升,而CD8含量则有所下降,与治疗前相比差异均有显著性意义（P〈0．05或P〈0．001）。【结论】祛风凉血法治疗慢性血热妄行型ITP的机理之一可能与其调节T淋巴细胞亚群及NK细胞水平有关。     

Modification of COL1A1 in Autologous Adipose Tissue-Derived Progenitor Cells Rescues the Bone Phenotype in a Mouse Model of Osteogenesis Imperfecta

Osteogenesis imperfecta (OI) is a congenital genetic disorder mainly manifested as bone fragility and recurrent fracture. Mutation of COL1A1/COL1A2 genes encoding the type I collagen are most responsible for the clinical patients. Allogenic mesenchymal stem cells (MSCs) provide the potential to treat OI through differentiation into osteoblasts. Autologous defective MSCs have not been utilized in OI treatment mainly because of their impaired osteogenesis, but the latent mechanism has not been well understood. Here, the relative signaling abnormality of adipose-derived mesenchymal stem cells (ADSCs) isolated from OI type I mice (Col1a1^+/−365 mice) was explored. Autologous ADSCs transfected by retrovirus carrying human COL1A1 gene was first utilized in OI therapy. The results showed that decreased activity of Yes-associated protein (YAP) due to hyperactive upstream Hippo kinases greatly contributed to the weakened bone-forming capacity of defective ADSCs. Recovered collagen synthesis of autologous ADSCs by COL1A1 gene modification normalized Hippo/YAP signaling and effectively rescued YAP-mediated osteogenesis. And the COL1A1 gene engineered autologous ADSCs efficaciously improved the microstructure, enhanced the mechanical properties and promoted bone formation of Col1a1^+/−365 mice after femoral bone marrow cavity delivery and might serve as an alternative source of stem cells in OI treatment. © 2021 American Society for Bone and Mineral Research (ASBMR).     

肥大细胞和组胺与十二指肠球部溃疡发病的关系

本文检测了十二指肠球部溃疡患者和慢性浅表性胃炎患者及正常人球、胃粘膜内肥大细胞和组胺的实验指标.结果显示治疗前球部溃疡活动期患者的肥大细胞病理形态改变与正常人有差别,与慢性胃炎患者也有程度上的不同;而且脱粒细胞数量高于正常人和慢性胃炎患者(P<0.001)。说明球部溃疡活动期患者球、胃粘膜内肥大细胞处于高度活化脱粒状态.治疗后溃汤愈合,肥大细胞由脱粒型转变为接近正常人的静止型细胞,脱粒细胞数量下降(P<0.001),部分组胺值高的患者治疗后组胺值下降(P<0.05).提示肥大细胞的病理形态学改变可能是球部溃疡重要的发病机制之一,同时部分球部溃疡患者的发病及愈合过程也可能与局部组胺含量增高变化有关。     

阻断肝脏神经和抑制库普弗细胞对移植鼠肝保护作用的观察

目的　研究移植肝库普弗细胞和交感神经在再灌注损伤发生中的作用 ,以及阻断供肝交感神经和抑制库普弗细胞对移植肝的保护机制。方法　 13 0对实验大鼠随机分为 4组 ,即正常对照组 (N组 )、氯化钆组 (C组 )、六甲胺组 (H组 )和六甲胺氯化钆组 (HC组 )。同等条件下 ,于肝移植术后 4,8,16,2 4h检测受体的肝功能、肝储备功能 ,并切取肝脏组织行光镜、电镜检查。结果　阻断供肝交感神经和抑制供肝库普弗细胞可明显改善移植肝的肝功能和肝储备功能 ,形态学变化也与之相符。结论　阻断供肝交感神经和抑制供肝库普弗细胞对移植肝有保护作用     

Tmem100- and Acta2-Lineage Cells Contribute to Implant Osseointegration in a Mouse Model

Metal implants are commonly used in orthopedic surgery. The mechanical stability and longevity of implants depend on adequate bone deposition along the implant surface. The cellular and molecular mechanisms underlying peri-implant bone formation (ie, osseointegration) are incompletely understood. Herein, our goal was to determine the specific bone marrow stromal cell populations that contribute to bone formation around metal implants. To do this, we utilized a mouse tibial implant model that is clinically representative of human joint replacement procedures. Using a lineage-tracing approach, we found that both Acta2.creERT2 and Tmem100.creERT2 lineage cells are involved in peri-implant bone formation, and Pdgfra- and Ly6a/Sca1-expressing stromal cells (PαS cells) are highly enriched in both lineages. Single-cell RNA-seq analysis indicated that PαS cells are quiescent in uninjured bone tissue; however, they express markers of proliferation and osteogenic differentiation shortly after implantation surgery. Our findings indicate that PαS cells are mobilized to repair bone tissue and participate in implant osseointegration after surgery. Biologic therapies targeting PαS cells might improve osseointegration in patients undergoing orthopedic procedures. © 2021 American Society for Bone and Mineral Research (ASBMR).