bone resorption

骨吸收
  • 文章类型: Journal Article
    这项横断面研究旨在评估决定口腔外科医生和牙周病医生选择进行立即种植牙的因素。
    从2024年1月6日至2024年2月29日进行了匿名调查。问卷在线分发给立陶宛专家-口腔外科医生和牙周病医生,进行植入手术的人。本次调查共包括186名专业人员。卡方检验,它的自由度用于分析变量。
    拒绝立即植入的主要原因是根尖周病变大于5毫米,91.7%的口腔外科医生和96.9%的牙周病医生报告。99.2%的口腔外科医师和92.3%的牙周病医师认为良好的美学和解剖结构的保存是有利的。在审美区,对于牙周病医生来说,选择方法的主要标准是拔牙窝软组织的定量和定性指标96.9%,而对于口腔外科医生-牙槽骨壁的形态为87.6%。只有43.1%的牙周医师和33.9%的口腔外科医生熟悉并使用拔牙槽形态评估分类来立即放置牙种植体。
    考虑到研究结果,建议调整大学的教学计划,并增加执行牙科植入程序的专家的知识,通过开展持续的教育计划。
    UNASSIGNED: This cross-sectional study aimed to evaluate the factors that determine the choice of oral surgeons and periodontists to perform immediate dental implant placement.
    UNASSIGNED: An anonymous survey was carried out from January 6, 2024 to February 29, 2024. The questionnaire was distributed online to Lithuanian specialists - oral surgeons and periodontists, who perform implantation procedures. A total of 186 professionals were included in this survey. Chi-square test, its degrees of freedom was used for the analysis of variables.
    UNASSIGNED: The main reason for refusing immediate implant placement is a periapical lesion greater than 5 mm, reported by 91.7% of oral surgeons and 96.9% of periodontists. Good aesthetics and preservation of anatomical structures are identified as an advantage by 99.2% of oral surgeons and 92.3% of periodontists. In the aesthetic zone, for periodontists, the main criterion for choosing a method is the quantitative and qualitative indicators of the soft tissue of the extraction socket 96.9%, and for oral surgeons - the morphology of the bone walls of the socket 87.6%. Only 43.1% of periodontists and 33.9% of oral surgeons are familiar with and use extraction socket morphology assessment classifications for immediate dental implant placement.
    UNASSIGNED: Taking into account study\'s results, it is recommended to adjust the teaching programs at Universities and to increase the knowledge of specialists performing dental implantation procedures, by carrying out continuous educational programs.
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  • 文章类型: Journal Article
    骨质疏松症,以破骨细胞骨吸收和成骨细胞骨形成失调为特征,在衰老过程中严重威胁人类健康。然而,骨质疏松症仍然没有好的治疗方法,所以这个方向需要我们持续的关注,迫切需要新药来解决这个问题。
    中药丹参单体磷酚酸(PA)能有效抑制破骨细胞生成和去卵巢骨质疏松。然而,溶解性差和缺乏靶向性严重限制了其进一步应用。已开发出一种新型的骨靶向纳米药物(PA@TLipo),通过在阿仑膦酸盐官能化的脂质体中包封波莫诺酸来重建骨质疏松的微环境。通过合成等一系列操作,净化,封装,和标签,PA@TLipo已经准备好了。此外,细胞毒性,通过细胞和动物实验验证了骨靶向和抗骨质疏松作用。
    在瞄准方面,PA@TLipo能有效聚集在骨组织上,减少骨丢失,就毒性而言,与非靶向脂质体相比,PA@TLipo可以增加骨靶向能力,从而减轻全身细胞毒性。此外,PA@TLipo在体外抑制破骨细胞形成和骨吸收,并减少卵巢切除引起的骨质疏松小鼠的骨丢失。
    在这项研究中,一种新的治疗剂被设计和制造来治疗骨质疏松症,由作为药物袋的脂质体材料组成,PA作为抗骨质疏松药物,和ALN作为骨靶向分子。我们的研究是第一个采用骨靶向递送系统为OVX引起的骨丢失递送PA,提供治疗骨质疏松症的创新解决方案。
    UNASSIGNED: Osteoporosis, characterized by dysregulation of osteoclastic bone resorption and osteoblastic bone formation, severely threatens human health during aging. However, there is still no good therapy for osteoporosis, so this direction requires our continuous attention, and there is an urgent need for new drugs to solve this problem.
    UNASSIGNED: Traditional Chinese Medicine Salvia divinorum monomer pomolic acid (PA) could effectively inhibit osteoclastogenesis and ovariectomized osteoporosis. However, its poor solubility and lack of targeting severely limits its further application. A novel bone-targeting nanomedicine (PA@TLipo) has been developed to reconstruct the osteoporotic microenvironment by encapsulating pomolic acid in alendronate-functionalized liposomes. Through a series of operations such as synthesis, purification, encapsulation, and labeling, the PA@TLipo have been prepared. Moreover, the cytotoxicity, bone targeting and anti-osteoporosis effect was verified by cell and animal experiments.
    UNASSIGNED: In the aspect of targeting, the PA@TLipo can effectively aggregate on the bone tissue to reduce bone loss, and in terms of toxicity, PA@TLipo could increase the bone target ability in comparison to nontargeted liposome, thereby mitigating systemic cytotoxicity. Moreover, PA@TLipo inhibited osteoclast formation and bone resorption in vitro and reduced bone loss in ovariectomy-induced osteoporotic mice.
    UNASSIGNED: In this study, a novel therapeutic agent was designed and constructed to treat osteoporosis, consisting of a liposome material as the drug pocket, PA as the anti-osteoporosis drug, and ALN as the bone-targeting molecule. And our study is the first to employ a bone-targeted delivery system to deliver PA for OVX-induced bone loss, providing an innovative solution for treating osteoporosis.
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  • 文章类型: Journal Article
    目的:使用新型三维打印个性化钛网(3D-PITM)用于引导骨再生(GBR),评估牙槽嵴增大的临床和影像学结果。
    方法:术前使用锥形束计算机断层扫描(CBCT)评估牙槽嵴缺损,然后增加具有圆形和纺锤形孔的高孔隙率3D-PITM。术后立即和愈合6个月后进行CBCT扫描。将这些扫描与术前扫描进行比较,以计算骨体积的变化,高度,和宽度,以及相应的吸收率。然后对结果进行统计分析。
    结果:共有21名患者参与了这项研究,涉及38个植入部位的牙槽隆起。经过6个月的康复,21例患者的平均骨增量量保持在489.71±252.53mm3,吸收率为16.05%±8.07%。对于38个植入部位,平均垂直骨增量为3.63±2.29mm,吸收率为17.55%±15.10%。设计植入平台的水平骨增量为4.43±1.85mm,吸收率为25.26%±15.73%。平台下方2mm的水平骨增量为5.50±2.48mm,吸收率为16.03%±9.57%。主要并发症是暴露于3D-PITM,发生率为15.79%。
    结论:用于GBR的新型3D-PITM可导致可预测的骨增强。在设计中适度的过度增强,适当的软组织管理,严格的随访有利于减少移植物吸收和暴露的发生率。
    OBJECTIVE: To assess the clinical and radiographic outcomes of alveolar ridge augmentation using a novel three-dimensional printed individualized titanium mesh (3D-PITM) for guided bone regeneration (GBR).
    METHODS: Preoperative cone-beam computed tomography (CBCT) was used to evaluate alveolar ridge defects, followed by augmentation with high-porosity 3D-PITM featuring circular and spindle-shaped pores. Postoperative CBCT scans were taken immediately and after 6 months of healing. These scans were compared with preoperative scans to calculate changes in bone volume, height, and width, along with the corresponding resorption rates. A statistical analysis of the results was then conducted.
    RESULTS: A total of 21 patients participated in the study, involving alveolar ridge augmentation at 38 implant sites. After 6 months of healing, the average bone augmentation volume of 21 patients remained at 489.71 ± 252.53 mm3, with a resorption rate of 16.05% ± 8.07%. For 38 implant sites, the average vertical bone increment was 3.63 ± 2.29 mm, with a resorption rate of 17.55% ± 15.10%. The horizontal bone increment at the designed implant platform was 4.43 ± 1.85 mm, with a resorption rate of 25.26% ± 15.73%. The horizontal bone increment 2 mm below the platform was 5.50 ± 2.48 mm, with a resorption rate of 16.03% ± 9.57%. The main complication was exposure to 3D-PITM, which occurred at a rate of 15.79%.
    CONCLUSIONS: The novel 3D-PITM used in GBR resulted in predictable bone augmentation. Moderate over-augmentation in the design, proper soft tissue management, and rigorous follow-ups are beneficial for reducing the graft resorption and the incidence of exposure.
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  • 文章类型: Journal Article
    目的:本研究旨在比较两种技术-无细胞真皮基质(ADM)移植和隆起技术(TT)-在植入物放置的同时增加软组织高度(STH)以最大程度地减少植入物周围骨水平(CBL)变化的功效。
    方法:纳入40例单下颌后牙颌无牙颌愈合部位软组织薄表型患者。20例患者同时接受植入植入ADM移植术,而其他人则接受了水下愈合基台(TT)。在修复分娩和1年随访时测量临床植入物周围软组织高度和影像学CBL变化。
    结果:两种技术都有效增加了软组织厚度,增强后的最终平均STH为3.4±0.5mm。平均而言,增强后,ADM组软组织增加1.6±0.5mm,TT组软组织增加1.8±0.4mm。在ADM组中,中CBL从0.4±0.3mm下降到0.1±0.2mm,远端CBL在1年内从0.5±0.3mm下降到0.2±0.3mm。在TT组中,mesialCBL在0.3±0.2mm处保持稳定,而远端CBL从0.5±0.5mm略微降低至0.3±0.2mm。两组的CBL变化很小,表明很大的稳定性(pmesial=0.003,pterial=0.004)。TT在预防中骨丢失方面特别有效(pmesal=0.019)。组间CBL改变显着不同(p=0.019),并且在远端部位没有明显的差异(p=0.944)。两种治疗均未在植入物肩部以下表现出明显的骨重建。
    结论:这项研究表明,这两种技术在增强STH方面都是成功的,它们可以有效地减少种植体周围骨水平的变化,TT略胜一筹。TT更容易发生术后并发症。该RCT在参与者招募和随机分组之前未注册。
    OBJECTIVE: This study aimed to compare the efficacy of two techniques-acellular dermal matrix (ADM) grafting and tenting technique (TT)-for soft tissue height (STH) augmentation simultaneous to implant placement to minimize peri-implant crestal bone level (CBL) changes.
    METHODS: Forty patients with a healed single mandibular posterior edentulous site with a thin soft tissue phenotype were enrolled. Twenty patients received simultaneously to implant placement ADM grafting, while the others received submerged healing abutment (TT). Clinical peri-implant soft tissue height and radiographic CBL changes were measured at restoration delivery and 1-year follow-up.
    RESULTS: Both techniques effectively increased soft tissue thickness, resulting in a final average STH of 3.4 ± 0.5 mm after augmentation. On average, soft tissue increased by 1.6 ± 0.5 mm in group ADM and by 1.8 ± 0.4 mm in group TT after augmentation. In Group ADM, mesial CBL decreased from 0.4 ± 0.3 mm to 0.1 ± 0.2 mm, and distal CBL decreased from 0.5 ± 0.3 mm to 0.2 ± 0.3 mm over 1 year. In Group TT, mesial CBL remained stable at 0.3 ± 0.2 mm, while distal CBL reduced slightly from 0.5 ± 0.5 mm to 0.3 ± 0.2 mm. Both groups showed minimal changes in CBL, indicating great stability (pmesial = 0.003, pdistal = 0.004). TT was particularly effective in preventing mesial bone loss (pmesial = 0.019). The mesial CBL changes significantly differed between groups (p = 0.019), and not significantly at distal sites (p = 0.944). Neither treatment exhibited significant bone remodeling below the implant shoulder.
    CONCLUSIONS: This study suggests that both techniques were successful in STH augmentation, and they may effectively reduce peri-implant crestal bone level changes, with TT being slightly superior. TT was more prone to post-surgical complications. This RCT was not registered before participant recruitment and randomization.
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  • 文章类型: Systematic Review
    目的:本系统综述旨在总结和综合研究肉毒杆菌毒素(BT)应用于咀嚼肌的继发性作用及其对骨密度的影响的证据。
    方法:数据库搜索一直进行到3月19日,2024.通过Cochrane工具对随机对照试验的偏倚风险和ROBINS-I工具对非随机研究进行评估。Cochrane建议评估开发和评估等级(GRADE)用于评估总体证据的置信度。
    结果:发现了五项关于肉毒杆菌毒素应用于咀嚼肌时对骨密度和再吸收的影响的研究。在观察肉毒杆菌毒素对下颌髁突体积的影响时,大多数研究均未观察到显着变化,密度,下颌角厚度,和冠状突体积。唯一具有统计学和临床相关性的发现是接受两次BT的患者与接受一次BT的患者之间的差异(SMD:-0.99[95CI:-1.94,-0.05])下颌角。
    结论:关于肉毒杆菌毒素的应用是否与骨吸收有关,尚无明确的模式。尽管一些研究显示了这些发现的统计学意义,骨密度变化的幅度及其临床意义尚不完全清楚。
    结论:为了了解将肉毒杆菌毒素用于咀嚼肌的有效性及其对下颌骨密度的可能的继发性不利影响。
    OBJECTIVE: This systematic review aims to summarize and synthesize the evidence that investigates the secondary effects of the application of botulinum toxin (BT) into the masticatory muscles and its effects on bone density.
    METHODS: Database searches were conducted until March 19th, 2024. The quality of the studies was assessed by the Cochrane tool risk of bias for the randomized controlled trials and the ROBINS-I tool for non-randomized studies. The Cochrane Grading of Recommendations Assessment Development and Evaluation (GRADE) was used to evaluate the confidence in the overall evidence.
    RESULTS: Five studies looking at the effects of botulinum toxin on bone density and resorption when applied to masticatory muscles were found. No significant changes were observed in most of the studies when looking at the effects of botulinum toxin on mandibular condyle volume, density, mandibular angle thickness, and coronoid process volume. The only finding that was statistically and clinically relevant was the difference between patients who received a double application of BT when compared with patients who received a single application (SMD: -0.99 [95%CI: -1.94,-0.05]) on the volume of the mandibular angle.
    CONCLUSIONS: There is no clear pattern on whether the application of botulinum toxin is associated with bone resorption or not. Although some studies show statistical significance of the findings, the magnitude of the changes in bone density and their clinical significance are not completely clear.
    CONCLUSIONS: To understand the effectiveness of the use of botulinum toxin into the masticatory muscles and its possible secondary adverse effects on the density of the mandible.
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  • 文章类型: Journal Article
    血管生成-成骨细胞-破骨细胞的不平衡系统被认为是骨重塑功能障碍疾病或骨整合丧失的主要因素。破骨细胞前体是加速骨特异性血管生成和维持正常成骨细胞和破骨细胞功能的关键细胞。氧化石墨烯是一种有效的支架表面改性剂,在骨组织工程中具有广阔的应用前景。然而,氧化石墨烯对破骨细胞与血管生成相互作用的影响尚未阐明。在这项研究中,建立大鼠颅骨缺损模型并用电化学衍生的纳米氧化石墨烯(ENGO)水凝胶处理。与对照组相比,在ENGO组中观察到更高的血管生成和前破骨细胞中的血小板衍生生长因子(PDGF)B。此外,体外实验证明,ENGO能显著降低核因子κB配体(RANKL)诱导的破骨细胞相关标志物受体激活剂的表达,并抑制骨吸收活性.此外,ENGO增强破骨细胞衍生的偶联因子PDGF-BB的分泌并促进血管生成。我们的研究揭示了异柠檬酸脱氢酶1(IDH1)在ENGO介导的破骨细胞分化和PDGF-BB分泌调节中的关键作用。IDH1表达的降低降低了组蛋白赖氨酸脱甲基酶7A(KDM7A)的水平,随后增加了组织蛋白酶K启动子区域中的H3K9me2水平。总之,我们发现ENGO通过抑制RANKL诱导的破骨细胞成熟和促进PDGF-BB分泌促进血管生成。这些结果表明,ENGO有望用于促进破骨细胞-内皮细胞串扰,为骨吸收和破骨细胞相关性骨丢失疾病的治疗提供了有效的策略。
    An imbalanced system of angiogenesis-osteoblasts-osteoclasts is regarded as the main factor in bone remodeling dysfunction diseases or osseointegration loss. Osteoclast precursors are the key cells that accelerate bone-specific angiogenesis and maintain normal osteoblast and osteoclast function. Graphene oxide is an effective scaffold surface modification agent with broad application prospects in bone tissue engineering. However, the effect of graphene oxide on the interaction between osteoclasts and angiogenesis has not yet been elucidated. In this study, a rat calvarial defect model was established and treated with an electrochemically derived nanographene oxide (ENGO) hydrogel. Higher angiogenesis and platelet-derived growth factor (PDGF) B in preosteoclasts were observed in the ENGO group compared with that in the control group. Moreover, in vitro experiments demonstrate the efficacy of ENGO in substantially reducing the expression of the receptor activator of nuclear factor-kappaB ligand (RANKL)-induced osteoclast-associated markers and inhibiting bone resorption activity. Additionally, ENGO enhances the secretion of the osteoclast-derived coupling factor PDGF-BB and promotes angiogenesis. Our investigation revealed the crucial role of isocitrate dehydrogenase 1 (IDH1) in the ENGO-mediated regulation of osteoclast differentiation and PDGF-BB secretion. The decreased expression of IDH1 reduces the level of histone lysine demethylase 7A (KDM7A) and subsequently increases the H3K9me2 level in the cathepsin K promoter region. In summary, we found that ENGO promotes angiogenesis by inhibiting the maturity of RANKL-induced osteoclasts and enhancing PDGF-BB secretion. These results indicate that ENGO holds promise for the application in fostering osteoclast-endothelial cell crosstalk, providing an effective strategy for treating bone resorption and osteoclast-related bone loss diseases.
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  • 文章类型: Journal Article
    目的:探讨不同义齿条件对全口义齿佩戴者咀嚼功能和患者报告结局指标(PROMs)的影响。
    方法:根据美国口腔修复学会(ACP)分类,选择60例无牙患者并分为两组:非萎缩性(NAT)(I类和II类)(n=24)和萎缩性(AT)(III类和IV类)(n=36)。所有患者均接受新的全口义齿(CD)。评估了客观变量(咀嚼性能和吞咽阈值)以及PROM(口腔健康相关生活质量(OHIP-EDENT),患者满意度)和假体质量,在基线(使用旧CD)和4个月后使用新的假体。数据通过Mann-Whitney检验和广义方程估计(GEE)进行分析,线性回归和卡方检验。
    结果:在两个时间点的NAT组中观察到更高的咀嚼性能(p<.05),基线和4个月后。然而,与基线相比,两组患者在4个月后表现出显著的咀嚼改善(p<.05)。4个月后满意度和总体生活质量改善,组间无差异(p>0.05)。关于CD的质量,AT组的基线结果显着降低(p<0.05),但4个月后,组间和组内分析均无显著差异(p>.05)。
    结论:义齿承载条件似乎影响咀嚼功能,但是PROM几乎没有受到影响。
    OBJECTIVE: To investigate the influence of different denture-bearing conditions on the masticatory function and patient-reported outcome measures (PROMs) of complete denture wearers.
    METHODS: Sixty edentulous patients were selected and allocated into two groups according to the American College of Prosthodontics\' (ACP) classification: non-atrophic (NAT) (Classes I and II) (n = 24) and atrophic (AT) (Classes III and IV) (n = 36). All patients received new complete dentures (CDs). The objective variables (masticatory performance and swallowing threshold) were assessed as well as the PROMs (oral health-related quality of life (OHIP-EDENT), patient satisfaction) and quality of the prosthesis, at baseline (using the old CD) and after 4 months new prostheses use. Data were analyzed by Mann-Whitney test followed by the Generalized Equations Estimation (GEE), linear regression and Chi-square test.
    RESULTS: Higher masticatory performance was observed in the NAT group (p < .05) for both time points, baseline and after 4 months. However, compared to baseline, both groups showed significant masticatory improvement after 4 months (p < .05). Satisfaction and overall quality of life improved after 4 months with no difference between groups (p > .05). Regarding the quality of the CD, baseline results were significantly (p < .05) lower in the AT group, but after 4 months, no significant differences were found between groups and in intragroup analysis (p > .05).
    CONCLUSIONS: The denture-bearing conditions seems to impact masticatory function, but the PROMs are barely affected.
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  • 文章类型: Journal Article
    这项荟萃分析旨在检查2型糖尿病(T2DM)患者和非T2DM对照组之间骨代谢生化指标的差异。
    两个独立的评估者搜索了五个数据库:PubMed,EMBASE,EBSCOhost,WebofScience,还有Cochrane图书馆.我们的目的是确定研究T2DM对骨代谢生化标志物影响的观察性研究。文献检索涵盖了从数据库建立到2022年11月的时期。如果他们使用横断面评估T2DM患者和非T2DM对照组之间骨代谢生化标志物的差异,队列,或病例对照研究设计。
    分析中包括14项研究,包括12项横断面研究和2项队列研究。与非T2DM对照组相比,2型糖尿病患者骨钙蛋白和P1NP水平降低,它们是骨形成的标志。相反,碱性磷酸酶和骨特异性碱性磷酸酶的水平,其他骨形成标记,增加。骨吸收标志物CTX显示水平下降,而TRACP则无显著性差异。
    在患有T2DM的个体中,大多数骨转换标志物表明骨转换速率降低。尽管骨矿物质密度较高,但这种减少会导致骨脆性增加。可能增加骨质疏松症的风险。
    系统审查注册:https://www。crd.约克。AC.uk/prospro/display_record.php?标识符CRD42022366430。
    UNASSIGNED: This meta-analysis aims to examine differences in biochemical markers of bone metabolism between individuals with type 2 diabetes (T2DM) and non-T2DM control groups.
    UNASSIGNED: Two independent evaluators searched five databases: PubMed, EMBASE, EBSCOhost, Web of Science, and the Cochrane Library. We aimed to identify observational studies investigating the impact of T2DM on biochemical markers of bone metabolism. Literature retrieval covered the period from the establishment of the databases up to November 2022. Studies were included if they assessed differences in biochemical markers of bone metabolism between T2DM patients and non-T2DM control groups using cross-sectional, cohort, or case-control study designs.
    UNASSIGNED: Fourteen studies were included in the analysis, comprising 12 cross-sectional studies and 2 cohort studies. Compared to the non-T2DM control group, T2DM patients showed reduced levels of Osteocalcin and P1NP, which are markers of bone formation. Conversely, levels of Alkaline phosphatase and Bone-specific alkaline phosphatase, other bone formation markers, increased. The bone resorption marker CTX showed decreased levels, while TRACP showed no significant difference.
    UNASSIGNED: In individuals with T2DM, most bone turnover markers indicated a reduced rate of bone turnover. This reduction can lead to increased bone fragility despite higher bone mineral density, potentially increasing the risk of osteoporosis.
    Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php? identifier CRD42022366430.
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  • 文章类型: Journal Article
    背景:上皮基质相互作用1(EPSTI1)在M1巨噬细胞中起重要作用,诱导破骨细胞生成。最近一项涉及426,824名个体的全基因组关联研究(GWAS)表明,EPSTI1与骨质疏松症密切相关(P<5E-8)。因此,我们推测EPSTI1通过破骨细胞的形成参与了骨质疏松的调节。EPSTI1在破骨细胞生成和骨吸收中的作用尚不清楚。
    方法:收集骨质疏松患者和对照组患者的股骨标本。免疫荧光染色用于检测EPSTI1和信号通路的表达。使用抗酒石酸酸性磷酸酶(TRAP)染色测试了Sh-EPSTI1慢病毒感染的RAW264.7细胞的破骨细胞潜能,西方印迹,和定量逆转录聚合酶链反应(qRT-PCR)。蛋白质印迹也用于检查信号传导途径。
    结果:在这项研究中,发现EPSTI1在骨质疏松患者骨切片的抗酒石酸酸性磷酸酶阳性(ACP5)破骨细胞中显着增加。接下来,我们确定EPSTI1是破骨细胞生成和破骨细胞分化能力的正调节因子。EPSTI1表达减少导致破骨细胞吸收减少。机械上,EPSTI1驱动的破骨细胞生成受NF-κB通路调控,它是由蛋白激酶R(p-PKR)的磷酸化介导的。此外,EPSTI1通过PKR/NF-κB途径参与骨质疏松的调节也在骨质疏松患者的骨样本中得到证实。
    结论:总的来说,我们的研究结果表明,EPSTI1可能通过PKR/NF-κB通路调节破骨细胞分化和骨吸收,需要体内实验进一步验证EPSTI1作为骨质疏松症的治疗靶点.
    BACKGROUND: Epithelial stromal interaction 1 (EPSTI1) plays an important role in M1 macrophages, which induce osteoclastogenesis. One recent genome-wide association study (GWAS) involving 426,824 individuals has shown that EPSTI1 is strongly associated with osteoporosis (P < 5E-8). Therefore, we speculate that EPSTI1 participates in the modulation of osteoporosis through osteoclastogenesis. The roles of EPSTI1 in osteoclastogenesis and bone resorption remain unclear.
    METHODS: Femur specimens were collected from osteoporotic patients and control patients. Immunofluorescence staining was used to detect the expression of EPSTI1 and signaling pathways. The osteoclastic potential of RAW264.7 cells with Sh-EPSTI1 lentivirus infection was tested using tartrate-resistant acid phosphatase (TRAP) staining, western blotting, and quantitative reverse transcription polymerase chain reaction (qRT-PCR). Western blotting was also used to examine signaling pathways.
    RESULTS: In this study, EPSTI1 was found to be significantly increased in tartrate-resistant acid phosphatase positive (ACP5+) osteoclasts of bone sections from osteoporotic patients. Next, we identified EPSTI1 as a positive regulator of osteoclastogenesis and osteoclast differentiation capability. Diminished EPSTI1 expression resulted in reduced osteoclastic resorption. Mechanistically, EPSTI1-driven osteoclastogenesis was regulated by NF-κB pathway, which was mediated by the phosphorylation of protein kinase R (p-PKR). Furthermore, EPSTI1 participating in the modulation of osteoporosis via PKR/NF-κB pathway was also verified in the bone samples of osteoporotic patients.
    CONCLUSIONS: Collectively, our findings suggest that EPSTI1 may regulate osteoclast differentiation and bone resorption through PKR/NF-κB pathway and in vivo experiments are needed to further verify EPSTI1 as the therapy target for osteoporosis.
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  • 文章类型: Journal Article
    脂联素,脂肪因子,调节代谢过程,包括葡萄糖通量,脂质分解,和胰岛素反应,通过激活脂联素受体1和2(AdipoR1和AdipoR2)。我们之前已经证明球状脂联素(gAd),脂联素的内源性形式,在绝经后骨量减少的啮齿动物模型中具有骨合成代谢和抗分解代谢作用。此外,我们报道了从脂联素的胶原结构域鉴定出一个13-mer肽(ADP-1),表现出显著的脂联素模拟特性。由于gAd的临床发展受到其大尺寸的制约,在这里,我们研究了ADP-1的成骨特性。ADP-1比gAd更有效地诱导成骨细胞分化。ADP-1通过两个参与脂联素受体参与的下游途径诱导成骨细胞分化。首先,它增强了线粒体生物发生和OxPhos,导致成骨细胞分化。其次,它激活了Akt-糖原合成酶激酶3β-Wnt通路,从而增加成骨细胞分化。此外,ADP-1抑制成骨细胞核κB配体受体激活剂的产生,使其能够充当双重作用分子(除了促进成骨细胞功能外,还抑制破骨细胞功能)。在骨质减少的卵巢切除大鼠中,ADP-1通过刺激骨形成和抑制骨吸收来增加骨量和强度并改善小梁完整性。此外,通过增加骨骼中三羧酸循环中产生ATP的中间体,ADP-1可能促进成骨细胞功能。鉴于其双重作用机制和高效力,ADP-1提供了一个独特的机会来解决未满足的临床需求,以将骨质疏松症中的异常骨重塑重置为正常。可能提供改善疾病的影响。
    Adiponectin, an adipokine, regulates metabolic processes, including glucose flux, lipid breakdown, and insulin response, by activating adiponectin receptors 1 and 2 (AdipoR1 and AdipoR2). We have previously shown that globular adiponectin (gAd), an endogenous form of adiponectin, has osteoanabolic and anti-catabolic effects in rodent models of postmenopausal osteopenia. Moreover, we reported the identification of a 13-mer peptide (ADP-1) from the collagen domain of adiponectin, which exhibited significant adiponectin-mimetic properties. Since the clinical development of gAd is constrained by its large size, here, we investigated the osteogenic property of ADP-1. ADP-1 induced osteoblast differentiation more potently than gAd. ADP-1 elicited osteoblast differentiation through two downstream pathways that involved the participation of adiponectin receptors. Firstly, it enhanced mitochondrial biogenesis and OxPhos, leading to osteoblast differentiation. Secondly, it activated the Akt-glycogen synthase kinase 3β-Wnt pathway, thereby increasing osteoblast differentiation. Additionally, ADP-1 suppressed the production of receptor-activator of nuclear kappa B ligand from osteoblasts, enabling it to act as a dual-action molecule (suppressing osteoclast function besides promoting osteoblast function). In osteopenic ovariectomized rats, ADP-1 increased bone mass and strength and improved trabecular integrity by stimulating bone formation and inhibiting bone resorption. Furthermore, by increasing ATP-producing intermediates within the tricarboxylic acid cycle in bones, ADP-1 likely fueled osteoblast function. Given its dual-action mechanism and high potency, ADP-1 offers a unique opportunity to address the unmet clinical need to reset the aberrant bone remodeling in osteoporosis to normalcy, potentially offering a disease-modifying impact.
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