伴2型糖尿病慢性牙周炎患者TNF-α基因携带频率的研究

目的:通过对伴2型糖尿病慢性牙周炎患者、不伴全身系统性疾病的慢性牙周炎患者以及健康对照组中TNF-α基因携带频率的分析,探讨病例组和对照组在该基因携带频率上的差异,并比较各组牙周临床指标和易感等位基因的关系。方法:采用牙周探针,对112例伴2型糖尿病慢性牙周炎患者(DM组)、99例单纯慢性牙周炎患者(CP组)以及健康对照组进行牙周临床指标检查和TNF-α-308基因型(TNF1/2)检测。采用SPSS13.0软件包对数据进行χ2检验和方差分析。结果:在DM组和轻中度CP组之间,轻中度DM组和重度CP组之间,重度DM组和轻中度CP组之间,重度DM组和重度CP组之间,TNF2的阳性基因型分布均有统计学差异(P<0.05)。携带等位基因TNF2的DM组和CP组的牙周探诊深度、临床附着丧失均分别显著高于只携带等位基因TNF1的DM组和CP组患者(P<0.05)。结论:携带TNF-α-308等位基因TNF2可能会增加人群牙周炎的易感性,并且在2型糖尿病和牙周炎协同作用过程中具有重要作用。     

慢性牙周炎牙龈组织细胞凋亡及凋亡相关蛋白Caspase-3的表达

目的:研究慢性牙周炎牙龈组织中细胞凋亡的发生情况和Caspase-3蛋白的表达,探讨其在慢性牙周炎病变发生中的意义。方法:应用脱氧核糖核苷酸末端转移酶介导的原位缺口末端标记法(TUNEL法)、免疫组织化学方法检测21例慢性牙周炎牙龈组织和21例健康牙龈组织中的细胞凋亡指数(apoptosis index,AI)及Caspase-3蛋白的表达。结果:慢性牙周炎组牙龈组织中细胞凋亡指数明显高于正常对照组(P<0.05)。与正常组相比,慢性牙周炎组牙龈组织中细胞caspase-3表达明显增强,两组间有显著性差异(P<0.05)。结论:慢性牙周炎病人牙龈组织细胞发生凋亡,且通过激活细胞凋亡信号传导途径中的Caspase-3而导致慢性牙周炎发生。     

基质金属蛋白酶-2在人慢性牙周炎肥大细胞上表达的研究

目的观察基质金属蛋白酶-2(matrix metalloproteinase-2,MMP-2)在慢性牙周炎牙龈组织中肥大细胞上的表达,探讨MMP-2-tryptase双阳性肥大细胞(mast cells,MCs)在慢性牙周炎发病机制中的作用。方法将45例参试者依据慢性牙周炎的病变程度分成3组:健康对照组15例;轻度牙周炎组15例;重度牙周炎组15例。牙龈标本经10%福尔马林液固定48 h;制作牙龈组织连续切片,HE染色,光学显微镜下观察组织学改变;采用免疫荧光双染色法,荧光显微镜下观察牙龈组织中MMP-2-tryptase双阳性MCs的表达情况。结果与健康对照组相比,轻度和重度慢性牙周炎组牙龈组织MMP-2-tryptase双阳性MCs密度均显著升高(P<0.01);重度慢性牙周炎组牙龈组织MMP-2-tryptase双阳性MCs密度显著高于轻度牙周炎组(P<0.05)。结论慢性牙周炎牙龈组织MMP-2-tryptase双阳性MCs密度与牙周炎病变程度的趋势相一致,MMP-2-tryptase双阳性MCs在牙周炎的进展中可能有促进作用。     

血管内皮生长因子在正常与牙周炎牙龈组织中的表达差异研究

目的 检测血管内皮生长因子(VEGF)在正常与牙周炎的牙龈组织中的表达差异。方法 采用免疫组化PV两步法,检测VEGF在20例健康成人与20例慢性中重度牙周炎患者的牙龈组织中的表达差异。结果 健康组牙龈组织VEGF表达局限于上皮的颗粒层与部分棘层,其下方的结缔组织呈弱阳性表达,实验组牙龈组织上皮全层及结缔组织均呈强阳性表达,实验组VEGF表达高于健康组,两组之间的差异具有统计学意义(上皮区P<0.01,结缔组织区P<0.05)。结论 VEGF可能参与了牙周炎牙周袋壁龈组织的病理改变过程,在牙周炎发生发展及修复机制中可能具有重要意义。     

伴2型糖尿病的慢性牙周炎牙周可疑致病菌的检测

目的 检测伴2型糖尿病(diabetes mellitus,DM)的慢性牙周炎(chronic periodontitis,CP)患者龈下菌斑中牙周可疑致病菌的种类和构成,从微生物学角度探讨牙周炎与DM的相互作用机制.方法 采集伴2型DM的CP患者154例(DM组)、不伴DM的单纯CP患者120例(CP组)及40名全身及牙周健康者(N组)的龈下集合菌斑,传统酚-氯仿法提取菌斑DNA,以牙龈卟啉单胞菌(Porphyromonas gingivalis,Pg),伴放线放线杆菌(Actinobacillus actinomycetemcomitans,Aa),具核梭杆菌(Fusobacterium nucleatum,Fn),中间普氏菌(Prevotella intermedia,Pi),福塞坦氏菌(Tannerella forsythia,Tf),齿垢密螺旋体(Treponema denticola,Td)为目标菌,应用以16SrRNA为基础的聚合酶链反应(PCR)技术对龈下菌群进行检测.结果 Pg、Aa、Fn、Pi、Tf、Td在DM组中均可检出;与CP组相比,在性别、年龄、牙周状况基本一致的情况下,轻度牙周炎者DM组Pi的检出率为35%(8/23),CP组为65%(13/20),两组间差异有统计学意义(P<0.05);重度牙周炎者DM组Pg、Aa、Tf的检出率分别为78%(72/92)、27%(25/92)、67%(62/92),CP组分别为58%(35/60)、17%(10/60)、43%(26/60),DM组均显著高于CP组,差异有统计学意义(P<0.05).同时,DM组Aa、Tf PCR产物的平均灰度值(average gradation,AVG)比值显著高于CP组,Pi的AVG比值明显低于CP组,P<0.05.结论 与单纯CP相比,伴2型DM的牙周炎患者龈下菌斑中Pg、Aa、Tf的数量增多,Pi的数量减少.     

伴2型糖尿病的慢性牙周炎牙周可疑致病菌的检测

目的 检测伴2型糖尿病(diabetes mellitus,DM)的慢性牙周炎(chronic periodontitis,CP)患者龈下菌斑中牙周可疑致病菌的种类和构成,从微生物学角度探讨牙周炎与DM的相互作用机制.方法 采集伴2型DM的CP患者154例(DM组)、不伴DM的单纯CP患者120例(CP组)及40名全身及牙周健康者(N组)的龈下集合菌斑,传统酚-氯仿法提取菌斑DNA,以牙龈卟啉单胞菌(Porphyromonas gingivalis,Pg),伴放线放线杆菌(Actinobacillus actinomycetemcomitans,Aa),具核梭杆菌(Fusobacterium nucleatum,Fn),中间普氏菌(Prevotella intermedia,Pi),福塞坦氏菌(Tannerella forsythia,Tf),齿垢密螺旋体(Treponema denticola,Td)为目标菌,应用以16SrRNA为基础的聚合酶链反应(PCR)技术对龈下菌群进行检测.结果 Pg、Aa、Fn、Pi、Tf、Td在DM组中均可检出;与CP组相比,在性别、年龄、牙周状况基本一致的情况下,轻度牙周炎者DM组Pi的检出率为35%(8/23),CP组为65%(13/20),两组间差异有统计学意义(P<0.05);重度牙周炎者DM组Pg、Aa、Tf的检出率分别为78%(72/92)、27%(25/92)、67%(62/92),CP组分别为58%(35/60)、17%(10/60)、43%(26/60),DM组均显著高于CP组,差异有统计学意义(P<0.05).同时,DM组Aa、Tf PCR产物的平均灰度值(average gradation,AVG)比值显著高于CP组,Pi的AVG比值明显低于CP组,P<0.05.结论 与单纯CP相比,伴2型DM的牙周炎患者龈下菌斑中Pg、Aa、Tf的数量增多,Pi的数量减少.     

牙龈癌微血管密度及血管内皮生长因子表达的意义

目的 :研究牙龈鳞状细胞癌组织中微血管密度 (MVD)及血管内皮生长因子 (VGEF)的表达和意义。方法 :采用CD3 4单克隆抗体和VEGF多克隆抗体 ,用免疫组化S -P法对 42例牙龈鳞状细胞癌标本进行免疫组化染色。结果 :牙龈癌组织MVD与正常牙龈组织MVD两者差异有显著性 (P <0 .0 0 5)。有淋巴结转移的牙龈癌MVD与无淋巴结转移的牙龈癌MVD ,两者之间差异有显著性 (P <0 .0 5)。牙龈癌组织中VEGF表达阳性率为 71.43 % ,正常牙龈组织中VEGF表达阳性率为 2 5.0 0 % ,两者之间差异有显著性 (P <0 .0 5)。有淋巴结转移组VEGF阳性率为 83 .3 3 % ,高于无淋巴结转移组VEGF阳性率 (66.67% ) ,两者之间差异无显著性 (P >0 .0 5)。VEGF阳性牙龈癌MVD高于VEGF阴性牙龈癌MVD ,两者之间差异有显著性(P <0 .0 2 )。结论 :肿瘤的血管生成在牙龈癌的发生过程中起一定作用。MVD与牙龈癌淋巴结转移及VEGF表达有密切联系     

槲皮素脂质体对糖尿病牙周炎大鼠牙周组织的作用及血清AGEs的影响

目的:通过对Ⅱ型糖尿病牙周炎大鼠进行槲皮素干预,观察大鼠牙周组织的组织学变化、牙槽骨吸收量、血糖值变化以及血清晚期糖基化终末产物(advanced glycation end products,AGEs)的变化,探讨槲皮素对糖尿病牙周炎大鼠牙周组织的保护作用.方法:40只雄性SD大鼠,随机分成4组:空白对照组(N组)、牙周炎对照组(P组)、糖尿病牙周炎非治疗组(DP组)和糖尿病牙周炎槲皮素治疗组(DP+Q组).N组正常喂养,P组建立牙周炎模型,DP组和DP+Q组建立糖尿病牙周炎模型,每组10只.建模成功后DP+Q组灌喂槲皮素脂质体,DP组灌喂空白脂质体,给药6周后测量各组血糖值,ELISA法测量血清AGEs含量,取上颌骨做牙周组织切片观察牙周组织病理变化,测量牙槽骨吸收量.结果:P组牙槽骨吸收量、牙周组织炎症水平高于N组(P<0.05);DP组血糖值、血清AGEs含量、牙周组织炎症程度、牙槽骨吸收量均高于N组和P组(P<0.05);DP+Q组大鼠血糖值、血清AGEs含量、牙周组织炎症水平、牙槽骨吸收量均低于DP组(P<0.05).结论:槲皮素对糖尿病牙周炎大鼠的牙周组织有保护效果,其作用机制与降低血糖值与血清AGEs含量有关.     

牙周基础治疗对Ⅱ型糖尿病伴牙周炎病人糖基化终产物的影响

目的:观察牙周基础治疗对Ⅱ型糖尿病伴慢性牙周炎病人牙周组织和血清中糖基化终产物(advanced glycation end of products,AGEs)变化的长期影响。方法:诊断为Ⅱ型糖尿病并伴有中等程度以上牙周炎的病人30例,分为进行牙周基础治疗的干预组15例(DM1组),未进行牙周基础治疗的未干预组15例(DM2组);分别在初诊和每次复诊治疗前记录2组的探诊深度(probing depth,PD)、附着丧失(attachment loss,AL)、空腹血精、AGEs指标。结果:经牙周基础治疗后,DM1组牙周临床指标均有明显改善;2组AGEs水平有不同程度升高(P<0.05);DM1组第21个月AGFs水平显著低于DM2组,有统计学意义(P<0.05)。结论:牙周基础治疗对Ⅱ型糖尿病伴慢性牙周炎病人的PD、AL、血糖水平、AGEs水平有显著的改善(P<0.05),并且有助于长期稳定。     

糖尿病与牙周炎治疗效果的相互影响

目的:探讨2型糖尿病与牙周炎治疗的相互影响。方法:随机选择患2型糖尿病伴中、重度慢性牙周炎的患者66名,其中联合治疗组(n=34)进行降糖和牙周基础治疗;糖尿病治疗组(n=32)进行单纯降糖治疗。观察比较两组治疗8周后牙周炎及糖尿病各相关指标。结果:治疗8周后,联合治疗组牙周炎症状明显改善,白细胞介素-1β降低,糖尿病症状也有明显改善,较治疗前相比均有显著性差异(P<0.05);糖尿病治疗组糖尿病与牙周炎症状均明显改善(P<0.05);联合治疗组牙周指标的改善明显优于糖尿病治疗组(P<0.05),但两组糖尿病指标的改善无显著差异(P>0.05)。结论:对于糖尿病伴慢性牙周炎的患者,糖尿病的有效控制有利于牙周炎症状的改善,糖尿病牙周联合治疗更有利于患者牙周炎症状的改善。     

牙周炎患者牙龈组织中IL-21表达的研究

目的：研究不同类型牙周炎患者牙龈组织中IL-21基因的表达,探讨其在牙周炎发病中的作用。方法：选择慢性牙周炎患者12例,侵袭性牙周炎8例,健康对照组8例,采用实时定量PCR方法定量检测IL-21 mRNA在牙龈组织表达情况。结果：慢性牙周炎、侵袭性牙周炎、健康对照组牙龈组织中均有IL-21 mRNA的表达,慢性牙周炎组和侵袭性牙周炎组IL-21 mRNA相对表达量分别为0.000534±0.000504和0.00602±0.000137,显著高于健康对照组0.000161±0.000352,差异有统计学意义(P<0.05)。慢性牙周炎和侵袭性牙周炎牙龈组织IL-21mRNA表达没有显著性差异（P>0.05）。结论：IL-21在慢性牙周炎发病机制中可能发挥重要作用。     

Expression of Leptin and Visfatin in Gingival Tissues of Chronic Periodontitis With and Without Type 2 Diabetes Mellitus: A Study Using Enzyme‐Linked Immunosorbent Assay and Real‐Time Polymerase Chain Reaction

Background: The aim of this study is to investigate the protein and gene expression of leptin and visfatin in gingival tissue from patients with chronic periodontitis (CP), patients with CP and type 2 diabetes mellitus (T2DM), and healthy individuals. Methods: The study includes 50 individuals: 10 healthy individuals, 20 patients with CP, and 20 patients with CP and T2DM. Plaque index, gingival index, probing depth, and clinical attachment loss were measured, and gingival biopsies were obtained. Leptin and visfatin protein expression in gingival tissues was determined using enzyme‐linked immunosorbent assay, and messenger RNA (mRNA) expression was measured via real‐time polymerase chain reaction. Results: The highest leptin mRNA and protein expression was observed in the control group and was significantly (P ≤0.05) different from the CP and CP+T2DM groups. Gingival tissues from patients with CP and T2DM had a significant increase in visfatin and a decrease in leptin gene and protein expression (P <0.05) compared with both controls and patients with CP. Conclusion: Expression of leptin and visfatin in the gingival tissues suggests a possible role for these adipokines in the pathogenesis of CP and T2DM.     

牙周基础治疗对2型糖尿病伴慢性牙周炎患者龈沟液丝氨酸蛋白酶抑制剂和肿瘤坏死因子-α水平的影响

目的 观察牙周基础治疗对2型糖尿病伴发或不伴发慢性牙周炎患者龈沟液(gingival crevicular flu-id,GCF)丝氨酸蛋白酶抑制剂(vaspin)和肿瘤坏死因子-α(TNF-α)水平的影响.方法 本研究包含60个研究对象,分为4组:15例2型糖尿病伴发慢性牙周炎患者为DM-CP组;15例慢性牙周炎不伴发2型糖尿病患者为CP组;15例牙周健康的2型糖尿病患者为DM组;15例牙周及全身系统均健康的个体为CTRL组.治疗前与牙周基础治疗8周后取样GCF并检测牙周临床指标.通过ELISA法检测GCF样本中vaspin和TNF-α的水平.结果 治疗前慢性牙周炎组GCF中vaspin和TNF-α水平显著高于牙周健康组(P<0.05),治疗后慢性牙周炎组GCF中vaspin和TNF-α水平显著降低(P<0.05).各组vaspin总量与TNF-α总量、糖化血红蛋白水平、牙龈指数以及探诊深度在统计学上存在正相关关系(P<0.05).结论 牙周基础治疗能明显降低慢性牙周炎患者GCF中vaspin和TNF-α的水平.提示GCF中vaspin和TNF-α可作为糖尿病、牙周炎诊断及其预后的炎性标志物.     

慢性牙周炎伴2型糖尿病患者龈沟液中脂联素水平的检测及意义

目的：探究牙周炎伴2型糖尿病患者龈沟液中脂联素水平及意义。方法：纳入慢性牙周炎伴糖尿病患者（DM&CP）、慢性牙周炎患者（CP）、健康对照者（H）各20例,记录其临床指标（SBI、PLI、PD 和 AL）,并收集龈沟液（GCF）样本,用龈沟液测量仪 periotron8000对 GCF 进行定量,用脂联素 ELISA 试剂盒检测样本中脂联素含量,比较组间检测指标的差异以及临床指标与 GCF 中脂联素水平的相关性。结果：DM&CP 组 GCF 中脂联素水平显著低于其他2组（P ＜0．05）,CP 患者龈沟液脂联素水平与牙周健康组相比无统计学差异（P ＞0．05）。GCF 中脂联素水平与临床指标 PD 值、AL 值有负相关性（P ＜0．05）,与 SBI、PLI 无明显相关（P ＞0．05）。结论：龈沟液中脂联素水平降低可能与 DM&CP 发生发展有关。     

Periodontal status and cytoplasmic enzyme activities in gingival crevicular fluid of type 2 diabetic and/or obese patients with chronic periodontitis

Type 2 diabetes mellitus and obesity are the most common nutritional disorders in developed and developing countries. Increased prevalence of periodontal disease is a well-known complication of type 2 diabetes mellitus (DM). As obesity is generally the first step toward type 2 diabetes mellitus, it is possible to find exacerbated periodontal disease in obese patients, also. The purpose of this cross-sectional study was to investigate the periodontal status and aspartate aminotransferase and lactate dehydrogenase enzyme activities in gingival crevicular fluid (GCF) of type 2 diabetic and/or obese chronic periodontitis patients. A total of 39 chronic periodontitis patients participated in the study. The study population was divided into four groups according to body mass index and type 2 DM status: 1) type 2 DM obese patients, n = 8; 2) type 2 DM patients, n = 12; 3) obese patients, n = 8; 4) systemically healthy control group, n = 11. Enzyme activities in gingival crevicular fluid and periodontal status were evaluated. No significant differences in age, gingival index, plaque index, aspartate aminotransferase and lactate dehydrogenase enzyme activities were observed, but probing depths were significantly higher in the DM groups than in the control group. Obesity did not seem to be a significant factor in any parameters evaluated. The present study showed increased probing depth values for the diabetic groups but failed to show any significant relation between obesity and enzyme activity or periodontal status. However, the slightly increased probing depth values in the obese groups might be a clue to an impaired immune response and predisposition to periodontitis in that patient group.     

Involvement of vascular endothelial growth factor, CD44 and CD133 in periodontal disease and diabetes: an immunohistochemical study

Aim: The aim of this study was to investigate the relationship between expression of angiogenic and regeneration markers and periodontal disease in subjects with/without diabetes mellitus.
Material and Methods: Immunohistochemical detection of vascular endothelial growth factor (VEGF), CD44 and CD133 was performed in 16 samples each of (1) healthy gingiva from non-diabetic subjects (controls), (2) gingiva from non-diabetic subjects with periodontitis, (3) gingiva from subjects with type 1 diabetes and periodontitis, (4) gingiva from subjects with type 2 diabetes and periodontitis.
Results: Diseased gingivae from patients with diabetes and periodontitis had greater clinical measures of periodontal disease than those with periodontitis only. VEGF expression was significantly enhanced in epithelial and endothelial cells from patients with periodontitis compared with controls ( p <0.05). Epithelial CD44 expression was strong in all groups, while CD44 was significantly enhanced ( p <0.05) in connective tissue cells from both diabetic groups. Epithelial and endothelial CD133 expression was comparable in all patients except those with type 2 diabetes and periodontitis, where it was not detected. Stromal CD133 expression was significantly lower in patients with type 2 diabetes and periodontitis and was increased in periodontitis patients ( p <0.05).
Conclusions: The involvement and high expression of VEGF, CD44 and CD133 in periodontal disease may predict a greater regeneration capacity of gingival tissue.     

Overexpression of interleukin-1beta and interleukin-6 may play an important role in periodontal breakdown in type 2 diabetic patients

BACKGROUND AND OBJECTIVE: This study evaluated whether the biochemical changes associated with type 2 diabetes modulate the expression of interleukin-1beta, interleukin-6, interleukin-8, and interferon-gamma in sites with chronic periodontitis. MATERIAL AND METHODS: Biopsies were harvested and divided into three groups: group 1, systemically and periodontally healthy subjects (n = 10); group 2, systemically healthy subjects with moderate-to-severe chronic periodontitis (probing depth > 6 mm) (n = 20); and group 3, type 2 diabetic subjects with periodontitis (n = 20). Cytokine levels were assessed in the gingival tissues by enzyme-linked immunosorbent assay analysis. RESULTS: Data analysis demonstrated that the interleukin-1beta, interleukin-6, interleukin-8, and interferon-gamma levels were higher in the presence of periodontal inflammation than in the absence of inflammation, regardless of systemic status. The interleukin-1beta and interleukin-6 levels were higher in diabetic subjects (group 3) than in systemically healthy patients with comparable types of periodontitis (group 2). No difference was observed for the interleukin-8 and interferon-gamma levels between groups 2 and 3. CONCLUSION: Within the limits of this study, it was concluded that type 2 diabetes was associated with increased expression of interleukin-1beta and interleukin-6 in periodontally inflamed tissues of diabetic patients, relative to nondiabetic subjects, and that such overexpression may be involved in the mechanisms by which type 2 diabetes enhances periodontal destruction.     

OPG、RANKL在2型糖尿病伴牙周炎大鼠牙槽骨中的表达

目的:探讨骨保护素(OPG)和核因子κB受体活化因子(RANKL)在2型糖尿病伴牙周炎大鼠模型中的表达水平.方法:46只Wistar雄性大鼠,随机分为健康组10只;单纯牙周炎组12只;2型糖尿病组12只;2型糖尿病牙周炎组12只;分别建模,免疫组织化学方法检测牙槽骨OPG、RANKL蛋白表达.结果:与健康组相比,OPG在2型糖尿病组、单纯牙周炎组、2型糖尿病伴牙周炎组表达水平依次降低,RANKL的表达水平依次增强;OPG及RANKL的表达除2型糖尿病牙周炎组与单纯牙周炎组间比较无差异外,其余组间比较有统计学意义(P＜0.05).结论:炎症可能导致破骨细胞及免疫细胞中RANKL的上调和成骨细胞中OPG的下调.     

Hyperglucose Contributes to Periodontitis: Involvement of the NLRP3 Pathway by Engaging the Innate Immunity of Oral Gingival Epithelium

Background: The NLRP3 inflammasome is essentially a family of intracellular innate immune sensors that can respond to bacterial challenge and initiate early host immunity responses. However, the involvement and possible molecular mechanism of the NLRP3 pathway in the context of chronic periodontitis (CP) and diabetes mellitus have yet to be fully elucidated. Methods: Gingival tissues were collected from patients with CP and/or type 2 diabetes mellitus (T2DM), and the expression of NLRP3 and interleukin (IL)‐1β was analyzed by immunohistochemistry. To explore the possible molecular mechanism, human gingival epithelial cells (HGECs) were established in vitro and challenged with lipopolysaccharide (LPS) and/or high glucose. High extracellular K⁺ was applied as an inhibitor of NLRP3. The NLRP3 pathway was analyzed by immunocytochemistry and quantitative polymerase chain reaction. Results: Compared with control individuals, NLRP3 and IL‐1β were significantly upregulated in oral gingival epithelium of patients with CP and/or T2DM (P <0.05). The expression of NLRP3 was significantly upregulated in HGECs when stimulated in vitro by LPS or high glucose (P = 0.00). The simultaneous stimulation of LPS and high glucose contributed to significant upregulation of NLRP3 expression versus LPS or high glucose alone (P = 0.00). Although expression of caspase 1 and IL‐1β protein were increased in HGECs when stimulated by LPS, they were partially inhibited after the NLRP3 was successfully blocked. Conclusion: For patients with T2DM and CP, hyperglycemic status may exacerbate the inflammation state of gingival tissue by activating the NLRP3 pathway, and this abnormal host inflammatory response may contribute to further tissue breakdown.