Stromal cell‐derived factor‐1/Exendin‐4 cotherapy facilitates the proliferation,migration and osteogenic differentiation of human periodontal ligament stem cells in vitro and promotes periodontal bone regeneration in vivo

ObjectivesStromal cell‐derived factor‐1 (SDF‐1) actively directs endogenous cell homing. Exendin‐4 (EX‐4) promotes stem cell osteogenic differentiation. Studies revealed that EX‐4 strengthened SDF‐1‐mediated stem cell migration. However, the effects of SDF‐1 and EX‐4 on periodontal ligament stem cells (PDLSCs) and bone regeneration have not been investigated. In this study, we aimed to evaluate the effects of SDF‐1/EX‐4 cotherapy on PDLSCs in vitro and periodontal bone regeneration in vivo.MethodsCell‐counting kit‐8 (CCK8), transwell assay, qRT‐PCR and western blot were used to determine the effects and mechanism of SDF‐1/EX‐4 cotherapy on PDLSCs in vitro. A rat periodontal bone defect model was developed to evaluate the effects of topical application of SDF‐1 and systemic injection of EX‐4 on endogenous cell recruitment, osteoclastogenesis and bone regeneration in vivo.ResultsSDF‐1/EX‐4 cotherapy had additive effects on PDLSC proliferation, migration, alkaline phosphatase (ALP) activity, mineral deposition and osteogenesis‐related gene expression compared to SDF‐1 or EX‐4 in vitro. Pretreatment with ERK inhibitor U0126 blocked SDF‐1/EX‐4 cotherapy induced ERK signal activation and PDLSC proliferation. SDF‐1/EX‐4 cotherapy significantly promoted new bone formation, recruited more CXCR4⁺ cells and CD90⁺/CD34^‐ stromal cells to the defects, enhanced early‐stage osteoclastogenesis and osteogenesis‐related markers expression in regenerated bone compared to control, SDF‐1 or EX‐4 in vivo.ConclusionsSDF‐1/EX‐4 cotherapy synergistically regulated PDLSC activities, promoted periodontal bone formation, thereby providing a new strategy for periodontal bone regeneration.     

NLRP3 regulates alveolar bone loss in ligature‐induced periodontitis by promoting osteoclastic differentiation

ObjectivesNLRP3 inflammasome is a critical part of the innate immune system and plays an important role in a variety of inflammatory diseases. However, the effects of NLRP3 inflammasome on periodontitis have not been fully studied.Materials and methodsWe used ligature‐induced periodontitis models of NLRP3 knockout mice (NLRP3^KO) and their wildtype (WT) littermates to compare their alveolar bone phenotypes. We further used Lysm‐Cre/Rosa^nTnG mouse to trace the changes of Lysm‐Cre⁺ osteoclast precursors in ligature‐induced periodontitis with or without MCC950 treatment. At last, we explored MCC950 as a potential drug for the treatment of periodontitis in vivo and in vitro.ResultsHere, we showed that the number of osteoclast precursors, osteoclast differentiation and alveolar bone loss were reduced in NLRP3^KO mice compared with WT littermates, by using ligature‐induced periodontitis model. Next, MCC950, a specific inhibitor of the NLRP3 inflammasome, was used to inhibit osteoclast precursors differentiation into osteoclast. Further, we used Lysm‐Cre/Rosa^nTnG mice to demonstrate that MCC950 decreases the number of Lysm‐Cre⁺ osteoclast precursors in ligature‐induced periodontitis. At last, treatment with MCC950 significantly suppressed alveolar bone loss with reduced IL‐1β activation and osteoclast differentiation in ligature‐induced periodontitis.ConclusionOur findings reveal that NLRP3 regulates alveolar bone loss in ligature‐induced periodontitis by promoting osteoclastic differentiation.     

Dwellings and workspaces at Strandvägen, 5600–5000 cal. BC

This paper describes identified workspaces and the manufacture of slotted bone points at the Late Mesolithic settlement Strandvägen in Motala, in eastern central Sweden. Several dwellings were documented, Dwelling 1 being typically round-oval in shape 9 × 5.5 meters, with a floor area covering 49.5 m². Radiocarbon dates fall between approximately 5600-5200 cal BC. A combined archaeological record, with lithics and bone artefacts as well as analyses of the osteological assemblage has shown that slotted bone tools with mounted lithic inserts have been produced adjacent of the dwelling. The spatial distribution of bone flakes, microblades, processed resin and slotted artefacts testify to a clearly and delimited craft area near the shoreline of the river Motala Ström. Analyses of the finds, e.g. birch bark resin and prepared bone preforms by direct percussion, also help in reconstructing the stages of manufacturing composite projectile points in this part of Eurasia.     

“Take My Bone Away?” Hypoxia and bone: A narrative review

To maintain normal cellular and physiological function, sufficient oxygen is required. Recently, evidence has suggested that hypoxia, either pathological or environmental, may influence bone health. It appears that bone cells are distinctly responsive to hypoxic stimuli; for better or worse, this is still yet to be elucidated. Hypoxia has been shown to offer potentially therapeutic effects for bone by inducing an osteogenic–angiogenic response, although, others have noted excessive osteoclastic bone resorption instead. Much evidence suggests that the hypoxic‐inducible pathway is integral in mediating the changes in bone metabolism. Furthermore, many factors associated with hypoxia including changes in energy metabolism, acid–base balance and the increased generation of reactive oxygen species, are known to influence bone metabolism. This review aims to examine some of the putative mechanisms responsible for hypoxic‐induced alterations of bone metabolism, with regard to osteoclasts and osteoblasts, both positive and negative.     

成人胫骨平台骨折的流行病学特征及其变化趋势的回顾性研究

摘要 目的：回顾性研究成人胫骨平台骨折的流行病学特征及其变化趋势。方法：以我院2014年1月至2019年12月期间收治的1193例成人胫骨平台骨折患者为调查研究对象,根据患者收治的时间将患者分为A组(2014年1月~2015年12月收治,n=369)、B组(2016年1月~2017年12月收治,n=394)、C组(2018年1月~2019年12月收治,n=430)。对三组患者进行统一的问卷调查,并对三组患者的年龄、职业、致伤原因、骨折分型进行归纳统计,分析探讨成人胫骨平台骨折的流行病学特征及其变化趋势。结果：2014年~2019年成人胫骨平台骨折总体流行病学特征：男性患者数量多于女性患者,年龄主要在40~59岁,以从事体力劳动患者居多,骨折致伤原因中主要以交通事故和室内活动跌倒损伤为主,骨折Schatzker分型中以II型、IV型为主。三组年龄对比有差异性,年龄有逐年升高的趋势(P<0.05)。三组性别比例有显著性差异,男女性别比例差异在逐年缩小(P<0.05)。三组患者在职业类型方面也有显著性差异（P<0.05）,但均以体力劳动者居多。在致伤原因中,A组患者以交通事故致伤为主,C组患者以室内活动跌倒损伤为主,组间对比有显著差异(P<0.05)。在骨折分型中,A组以IV型为主,C组以II型为主(P<0.05)。结论：2014年至2019年成人胫骨平台骨折中男性较多,年龄以40~59岁为主,体力劳动者为高发职业,交通事故和室内活动跌倒损伤是最常见的致伤原因,好发骨折分型为Schatzker II型、IV型。变化趋势表现为骨折发病人数逐年上升,发病年龄有老龄化趋势,致伤原因和骨折分型也在逐渐变化。     

股前外侧穿支皮瓣与胸腹带蒂皮瓣对手外伤组织缺损修复的应用效果及对创面愈合程度的影响

摘要 目的：探讨股前外侧穿支皮瓣与胸腹带蒂皮瓣对手外伤组织缺损修复的应用效果及对创面愈合程度的影响。方法：选取我院2018年12月到2020年12月共收治的119例手外伤组织缺损患者作为研究对象,随机分为2组,分别为对照组（n=59,应用胸腹带蒂皮瓣修复术）和观察组（n=60,应用股前外侧穿支皮瓣修复术）。对比两组患者治疗优良率,对比两组患者治疗前后手部创面面积、创面愈合程度以及组织愈合时间,对比两组患者治疗后的Jamar握力、TAM和DASH评分情况,对比两组患者的皮瓣成活率、皮瓣危象率和血管吻合时间。结果：通过对比两组患者治疗优良率发现,观察组患者优的人数为21例、良为35例,优良率为93.33%,对照组患者优的人数为16例,良为30例,优良率为77.97%,观察组高于对照组（P＜0.05）;治疗后,与对照组相比,观察组患者的手部创面面积、组织愈合时间和DASH评分显著减少,创面愈合程度以及TAM与Jamar握力显著增加（P＜0.05）;通过对比两组患者的皮瓣成活率、术后皮瓣危象率以及血管吻合时间发现,两组患者的术后皮瓣危象率、血管吻合时间对比无明显差异（P＞0.05）,两组患者的术后皮瓣成活率对比差异显著,观察组明显高于对照组（P＜0.05）。结论：对手外伤组织缺损患者应用股前外侧穿支皮瓣与胸腹带蒂皮瓣修复术均具有明显的修复效果,但是应用股前外侧穿支皮瓣能够提升治疗效果,提升患者创面愈合程度减少愈合时间,提升患者手部运动情况,提升术后皮瓣成活率,值得临床应用推广。