甲状旁腺激素相关蛋白调控下颌髁突软骨的研究进展

下颌髁突软骨(MCC)不同于生长板和身体其他部位的关节软骨,属于继发性纤维软骨,是颞下颌关节的重要组成部分.由于下颌骨附有牙齿行使咀嚼功能的特殊性,MCC在一生中受机械刺激影响不断改建,随年龄增长可能发生退行性变.甲状旁腺激素相关蛋白(PTHrP)最早在恶性体液性高钙血症中发现,在许多组织中以旁分泌或者自分泌的方式发挥...     

髁突与生长板软骨发育早期组织学特征的比较研究

目的探讨髁突软骨与生长板软骨发育早期组织学特征上的异同,进一步了解髁突软骨的发育过程和生长特点,为临床上功能矫形的治疗提供理论依据。方法选用胚胎SD大鼠的髁突软骨与生长板软骨作为研究对象,建立发育早期的动物模型,对两种软骨进行组织切片染色观察,比较它们组织学特征上的异同。结果胎龄14~19 d,髁突软骨与生长板软骨的组织结构大体相似,但存在一定的差异。两种软骨分层不同,细胞形态不同,生长板增殖层和前肥大层软骨细胞更为扁平;细胞排列不同,生长板软骨细胞平行于长骨呈柱状排列,髁突软骨细胞分层排列,无细胞柱;另外,生长板软骨中肥大软骨细胞的出现较髁突软骨早。结论发育早期,髁突软骨与生长板软骨组织结构大体相似,但在软骨细胞分层、形态及排列方式方面存在一定差异。     

甲状旁腺激素相关蛋白在下颌骨髁突软骨生长发育中的作用机制

下颌骨髁突软骨是一种继发性纤维性软骨,其生长发育的调控过程可能更加复杂.近十几年来,国内外才渐有针对髁突软骨生长发育研究的相关报道.甲状旁腺激素相关蛋白(parathyroid hormone related protein,PTHrP)是软骨代谢的关键调控因子,广泛参与软骨生长改建、形态发生及软骨内成骨的过程.同四肢...     

甲状旁腺相关蛋白对鼠胚髁突软骨细胞增殖和分化的调控

目的 探讨甲状旁腺相关蛋白（PTHrP）对鼠胚髁突软骨细胞增殖和分化的影响。方法 在体外分离培养鼠胚髁突软骨细胞的基础上,观察PTHrP对其软骨结节形成、碱性磷酸酶（ALP）活性等的影响。结果 研究发现加入浓度分别为0.01 nmol/L、0.1 nmol/L、1 nmol/L、10 nmol/L的PTHrP后,0.01 nmol/L组与对照组相比,形成的软骨结节数量在统计学上无显著性差异（P>0.05）,而软骨结节数量从0.1 nmol/L组开始与对照组相比明显增加,统计学上
有显著性差异（P<0.05）。而ALP活性在0.1-10 nmol/L组与对照组相比明显升高,统计学上有显著性差异（P<0.05）。阻断其受体后,实验组和对照组软骨结节形成的数目明显减少（P<0.05）,而对其ALP活性的影响在实验组和对照组之间无显著性差异（P>0.05）。结论 PTHrP通过其受体具有促进髁突软骨细胞增殖和分化的作用,其调控机制与其在生长板软骨细胞及下颌膜内成骨中的作用相似。     

不同咀嚼负荷对幼兔髁突软骨内印度豪猪蛋白-人甲状旁腺激素相关蛋白通路表达的影响

目的 分析不同咀嚼负荷作用下,幼兔髁突软骨内印度豪猪蛋白（Ihh）-人甲状旁腺激素相关蛋白（PThrP）通路表达的差异性,探讨咀嚼应力负荷对髁突软骨Ihh-PThrP信号通路的影响。方法 选取10 d龄幼兔48只,随机分为硬食组和软食组,分别喂以同种颗粒状（硬食）和粉状（软食）,于饲养的第2、4、6、8周处死。采用苏木精-伊红（HE）染色、免疫组织化学、免疫印迹、实时定量荧光聚合酶链反应检测Ihh和PThrP mRNA和蛋白的动态变化。结果 HE染色显示硬食组髁突软骨厚度高于软食组的厚度;第2、4、6、8周,Ihh蛋白、PThrP蛋白和mRNA表达量在两组中呈递减趋势;软食组中Ihh和PThrP蛋白以及mRNA表达量显著低于硬食组。结论 较低的咀嚼负荷会造成髁突软骨生长因子Ihh和PThrP分泌减少,Ihh-PThrP通路表达迟缓,软骨发育受阻碍;适当的咀嚼负荷对髁突的正常发育有至关重要的作用。     

甲状旁腺激素受体1在大鼠颞下颌关节炎髁突软骨中的表达变化研究

目的 研究甲状旁腺激素受体1(parathyroid hormone receptor 1,PTH1R)在大鼠颞下颌关节骨关节炎（temporomandibular joint osteoarthritis,TMJOA）髁突软骨中的表达变化。方法 研究于2022年7月至2023年1月在潍坊医学院动物实验中心和潍坊市口腔生物医学重点实验室进行。选取8周龄健康雄性SD大鼠48只,将大鼠随机分为实验组和对照组,每组各24只。实验组大鼠用咬合升高法构建TMJOA动物模型,并于造模后的第2、4、6、8周分别处死6只大鼠,解剖分离双侧髁突;对照组大鼠仅进行相同时长的张口动作,其余操作与实验组相同。通过苏木精-伊红和番红O-固绿染色,观察大鼠髁突软骨的组织学变化,按照改良Mankin评分系统对大鼠髁突软骨及软骨下骨拍照并评分;再应用实时定量PCR(quantitative real-time PCR,qRT-PCR)和免疫组化染色,检测大鼠髁突软骨内PTH1R mRNA和蛋白的表达情况。结果 苏木精-伊红和番红O-固绿染色结果显示,所有时间点对照组髁突软骨的组织学形态具有一致性,而实验组颞下颌关节的...     

甲状旁腺相关蛋白在鼠胚髁突外植体软骨内成骨中的作用

目的探讨甲状旁腺相关蛋白(PTHrP)对体外培养的鼠胚髁突软骨内成骨的影响。方法体外解剖分离鼠胚髁突,行外植体培养,通过组织学、免疫组化等方法观察PTHrP对体外培养的髁突外植体软骨内成骨的影响。结果髁突外植体在无血清半固态培养系统中能正常发育。加入人PTHrP(1-34)后,实验组髁突长度的增加较对照组明显,两组间差异有显著性(P<0.05);组织学及免疫组化染色显示:加入人PTHrP(1-34)后培养的髁突外植体增殖层和肥大软骨细胞层明显增厚,同时Ⅱ及Ⅹ型胶原在增殖层和肥大软骨细胞层中表达增强。结论PTHrP可刺激髁突外植体软骨增殖层和肥大层软骨细胞的增殖,促进髁突软骨内成骨的形成。?     

甲状旁腺相关蛋白与软骨内成骨

甲状旁腺相关蛋白是近年来发现的对骨的形成有重要的作用的生长因子，本文主要对其在软骨内的表达，软骨内嘏骨的作用及其机制，信号传导途径等方面进行综述。     

经颧弓后上牵引下颌后髁突软骨中PTHrP的表达及意义

目的:观察经颧弓后上牵引下颌后兔颞下颌关节髁突软骨中PTHrP的分布特征,探讨PTHrP在髁突软骨改建过程中的作用。方法:手术在颧弓和下颌角之间放置弹簧持续地将兔右侧下颌骨向后上方牵引,分别于术后2、4、6周处死动物,观察实验组与对照组PTHrP的分布特征。结果:经颧弓后上牵引下颌,髁突受到过度负荷后髁突软骨发生改建。经颧弓后上牵引2周,增殖层和上肥大层软骨细胞PTHrP表达明显增强,而4和6周PTHrP表达强度不均,软骨细胞丛附近软骨细胞前体细胞内PTHrP表达较强。对照组PTHrP在整个实验过程中均处于弱表达。结论:PTHrP可能与髁突软骨的修复性改建密切相关。     

甲状旁腺素相关蛋白和甲状旁腺素及其Ⅰ型受体在髁突发育中的作用

髁突软骨是下颌骨重要的生长点,其细胞具有特殊的生长和分化方式。甲状旁腺素相关蛋白在髁突整个发育过程中起关键调节作用。甲状旁腺素作为最有前景的促骨合成代谢调节剂,在人工调节髁突发育中起着不可取代的作用。下面就甲状旁腺素相关蛋白和甲状旁腺素及其Ⅰ型受体在髁突发育中的研究进展作一综述。     

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髁突软骨和生长板软骨是不同部位的两种软骨,其发育过程均为软骨内成骨。下颌髁突软骨是继发性软骨,由纤维软骨构成;生长板软骨为原发性软骨,由透明软骨构成。二者行使的生理功能不同,在胚胎发生、生长特性、组织结构、软骨细胞的终末方式及对生长因子的反应等方面存在差异。本文就此差异对比做一综述。     

微RNA在下颌髁突软骨生长发育中作用的研究进展

微RNA(micro RNA,miRNA)是一类小的非编码单链RNA,通过与信使RNA结合发挥其生物学作用。研究显示miRNA可能在调节下颌髁突软骨的生长发育中起重要作用。本文就miRNA的产生及其作用机制,对下颌髁突软骨生长发育相关的miRNA研究进展进行综述,以期助于进一步研究下颌髁突软骨生长发育。     

机械应力作用下髁突生长因子表达的研究进展

髁突是下颌骨的重要生长区之一。髁突的生长与外界机械刺激高度相关，因此在正畸治疗中，功能矫治器通过引导下颌髁突的生长来矫治下颌骨发育不足，但对功能矫治器的作用机制一直存在争议。大量的实验证明机械应力引起组织代谢变化，生长因子及其它信号分子表达上调或下降，从而调控髁突细胞的生长与分化。本文对机械应力下髁突生长因子的变化及其作用作一综述。     

Postnatal expression of chondrogenic and osteogenic regulatory factor mRNA in the rat condylar cartilage

ObjectivesThe condylar cartilage is a key site of growth and development of the mandible. The aim of this research was to determine the mRNA expression levels of a number of chondrogenic and osteogenic regulatory factors in the condylar cartilage of the postnatal rat.Materials and methodsCondyles were extracted from 40 rats aged 4, 10, 21 or 90 days with 10 rats assigned to each age group. The condyles from one rat from each age group was fixed and decalcified in 10% EDTA for histology. Using cryogenic grinding combined with QIAzol reagent total RNA was purified from pooled samples collected for each age group. Each pool contained six condyles (N = 3). mRNA expression levels for 28 genes were determined using qPCR.ResultsHistological analysis revealed distinct morphological differences in the condyle tissue of the 4, 10, 21 and 90 day old postnatal rats. Expression of all examined genes was detected. High levels of mRNA for Alpl, Bglap, Col1a1, Col2a1, Runx2, Sox9 and Sp7 but not Msx1 were detected. Fgf1 and Fgf2 were expressed at a similar level. No significant difference (defined as ± fold-regulation > 2 and P < 0.05) in the gene mRNA expression levels was found when days 10, 21 or 90 were compared to day 4.ConclusionsApparent morphological changes of the rat condylar cartilage are not reflected in a change in the expression levels of the chondrogenic and osteogenic regulatory factor mRNA investigated in this study.     

RUNX蛋白在不同发育时期小鼠髁状突中的表达

目的：探索小鼠髁状突形态发育及此过程中RUNX蛋白的表达变化及意义。方法：取胚胎14．5d（E14．5）至出生后7．5d（P7．5）的小鼠下颌骨,制备髁突矢状位切片,苏木素一伊红（HE）染色观察。免疫组化方法检测RUNX蛋白表达分布。结果：E14．5开始,髁突间充质细胞聚集,而后逐渐分化出完整的软骨细胞分层,髁突逐渐由半圆变扁平。免疫组化示RUNXl、2阳性信号主要位于增殖层、前软骨细胞层及部分肥大层细胞,RUNX3阳性信号主要位于前软骨细胞层及肥大层。髁突前后部,RUNXl、2在前软骨细胞层的信号强度较肥大层更高。RUNX整体的表达呈现双峰曲线。结论：髁突前后部成熟较晚,更易发生改建。RUNXl、2协同作用于软骨细胞分化早期,RUNX3调节作用于软骨细胞成熟期。     

雌二醇浓度对大鼠髁突软骨细胞中雌激素受体mRNA表达的影响

目的：探讨雌二醇(estradiol,E2)对体外培养的髁突软骨细胞雌激素受体(estrogen recerptor,ER)基因表达的影响。方法：体外培养大鼠髁突软骨细胞,分别加入浓度为10-12、10-9、10-6、10-3 mmol/L的17β E2 24 h,实时定量PCR法检测所培养的髁突软骨细胞 ERα、ERβmRNA的表达。采用SPSS10.0软件包对结果进行统计学分析。结果：ERα和ERβ在体外培养的髁突软骨细胞中均有表达,17β E2能够上调ERα的基因表达,同时下调ERβ表达。在10-9 mmol/L的17β E2作用下,上调ERα基因表达最为明显。结论：E2浓度的改变可上调ERα的表达并下调ERβ的表达,在生理范围的雌激素浓度下,E2上调ERα基因表达的作用最为明显。     

Distribution of insulin-like growth factor-I mRNA in the mandibular condyle and rib cartilage of the rat during growth

This study makes a molecular biological comparison of primary and secondary cartilage at an early phase of postnatal development. The distribution of insulin-like growth factor-I (IGF-I) mRNA expression in the mandibular condyle and rib cartilage of 1-28-day-old rats was examined after in situ hybridisation using an oligo probe cocktail for IGF-I mRNA. In the condyle, expression was localised to a narrow strip under the articular layer where the cells are undifferentiated. Essentially, no differences were found in IGF-I synthesis within three samples from the same age group or between different age groups. In rib cartilage, IGF-I mRNA was localised within the germinative, proliferative and early hypertrophic cell layers in 1-28-day-old rats. Again, there were no differences in expression among animals of the same age or as a function of age. This pattern of IGF-I mRNA expression indicates that IGF-I synthesis during growth of the mandibular condylar cartilage is different from that of costal cartilage. The findings shed light on the problem of overgrowth often associated with the use of costochondral grafts to replace defective mandibular condyles.     

Influence of growth hormone on the mandibular condylar cartilage of rats

Growth hormone (GH) stimulates mandibular growth but its effect on the mandibular condylar cartilage is not well understood. OBJECTIVE: This study was designed to understand the influence of GH on mitotic activity and on chondrocytes maturation. The effect of GH on cartilage thickness was also determined. DESIGN: An animal model witt differences in GH status was determined by comparing mutant Lewis dwarf rats with reduced pituitary GH synthesis (dwarf), with normal rats and dwarf animals treated with GH. Six dwarf rats were injected with GH for 6 days, while other six normal rats and six dwarf rats composed other two groups. Mandibular condylar tissues were processed and stained for Herovici's stain and immunohistochemistry for proliferating cell nuclear antigen (PCNA) and alkaline phosphatase (ALP). Measurements of cartilage thickness as well as the numbers of immunopositive cells for each antibody were analysed by one-way analysis of variance. RESULTS: Cartilage thickness was significantly reduced in the dwarf animals treated with GH. PCNA expression was significant lower in the dwarf rats, but significantly increased when these animals were treated with GH. ALP expression was significant higher in the dwarf animals, while it was significantly reduced in the dwarf animals treated with GH. CONCLUSIONS: The results from this study showed that GH stimulates mitotic activity and delays cartilage cells maturation in the mandibular condyle. This effect at the cellular level may produce changes in the cartilage thickness.