下颌牵张成骨中髁突Ⅲ型胶原的免疫组化研究

目的 :观察下颌牵张成骨中髁突胶原的变化特征 ,探讨牵张成骨对关节软骨的影响。方法 :采用sabc免疫组化方法检测幼年狗在下颌双侧牵张成骨固定期的不同阶段 (0周、2周、4周、8周 )Ⅲ型胶原分布及含量的变化。结果 :Ⅲ型胶原的表达随时间的延长逐渐增加 ,至 4周达到顶峰 ,随后逐渐减弱。结论 :在下颌双侧牵张成骨中 ,幼年狗颞下颌关节发生适应性改建 ,表现为软骨细胞合成及分泌胶原的能力发生改变。     

不同剂量转化生长因子-β1对兔颞下颌关节骨关节炎的影响

探讨关节腔内注射不同剂量转化生长因子-β1（TGF-β1）对兔颞下颌关节骨关节炎（TMJOA）的影响。方法40只新西兰白兔,随机分为实验组（36只）和对照组（4只）。实验组通过双侧颞下颌关节盘部分切除建立骨关节炎模型,术后4周分别注射20、40和80 ng TGF-β1于右侧颞下颌关节内,左侧关节注射等量生理盐水。注射后6周及12周时,分批处死实验组与对照组动物。获取髁突标本后对软骨与软骨下骨分别行Micro CT检查与糖蛋白含量检测（番红-O染色）。结果 术后生理盐水组的关节呈明显的骨关节炎表现,其软骨糖蛋白含量较正常组明显降低,软骨下骨逐渐硬化。注射后6周,所有TGF-β1组糖蛋白含量均高于正常组与盐水组。其中,40 ng与80 ng组糖蛋白含量更高于20 ng组。注射后12周时,所有TGF-β1组关节软骨组织结构有序,其糖蛋白含量无组间差异,虽较6周时有所降低,但仍高于正常组。所有TGF-β1组的软骨下骨都得到显著改善,且具有与正常组类似的软骨下骨细微结构。结论 关节腔内注射TGF-β1能够有效地促进TMJOA中病变软骨的修复并阻止软骨下骨异常骨改建。     

颞下颌关节疾病

小鼠听骨关节、镫骨前庭关节和下颌关节发育过程中的形态学观察；双侧下颌牵张成骨对转化生长因子β1在颞下颌关节髁突表达的影响；突发性严重绞锁颞下颌关节的压力测量和分析；稳定性（he）垫治疗颞下颌关节可复性盘前移位的疗效分析；5种不同张口位的颞下颌关节区三维有限元模型的建立；……[编者按]     

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...     

不同年龄小鼠下颌髁突软骨双侧前牙对反(牙合)的响应

目的:探究不同年龄小鼠下颌髁突软骨对双侧前牙反■的响应以及甲状旁腺激素相关多肽(PTHrP)在该过程中与髁突软骨细胞分化的相关性。方法:选取6周龄小鼠(小龄)和28周龄小鼠(大龄)各42只。将各年龄组小鼠随机均分为3个对照组(3周组，7周组，11周组)和4个实验性双侧前牙反■实验组(3周组，7周组，11周组，7+4周组)。通过化学染色、免疫荧光染色以及免疫组织化学染色，观察颞下颌关节髁突软骨表型的变化以及PTHrP和骨钙素(OCN)的表达变化。结果:实验性双侧前牙反■能够诱导小鼠髁突出现骨关节炎(OA)样退变，大龄组更严重，去除咬合刺激可促进髁突软骨表型的恢复，小龄组明显。从3周开始，实验性双侧前牙反■组髁突软骨中PTHrP的表达开始降低，而OCN的表达水平明显升高。去除实验性双侧前牙反■后，小龄小鼠髁突软骨中PTHrP表达有明显升高，OCN的表达明显的降低，而大龄小鼠髁突软骨中PTHrP和OCN的表达水平变化不明显。结论:与大龄小鼠相比，小龄小鼠下颌髁突软骨对反■的响应较轻，去除反■刺激后髁突软骨的恢复能力较强。     

牵张成骨延长一侧下颌骨对颞下颌关节的影响

目的：研究牵张成骨（DO）延长一侧下颌骨对双侧颞下颌关节（TMJ）的影响。方法：用DO技术将8只山羊的一侧下颌骨延长10mm，在牵张完成后第8和16周分别处死4只动物，取双侧关节作组织学和扫描电镜研究。结果：下颌一侧DO术后双侧髁状突发生适应性改建，髁突表面超微结构正常。结论：在适当的牵张条件下延长一侧下颌骨不会对TMJ造成病理性损害。     

关节盘穿孔致大鼠颞下颌关节骨关节病的形态学及组织病理学观察

目的通过关节盘穿孔建立大鼠颞下颌关节骨关节病(temporomandibular joint osteoarthrosis,TMJOA)模型,并观察颞下颌关节(temporomandibular joint,TMJ)髁突的形态学特征及组织病理学变化。方法8只12周龄雄性SD大鼠购自重庆医科大学,体质量200~250 g,通过随机数表法将其分为1周组和4周组,每组各4只。用齿科慢机球钻在每只大鼠左侧(模型侧)关节盘中后部形成直径1.5 mm的规则圆形穿孔,右侧(对照侧)不予处理。1周组和4周组大鼠分别于处理后1、4周时处死,获取双侧TMJ组织,通过形态学观察、影像学检查分析关节软骨的退化程度及软骨下骨的结构变化。通过免疫组织化学染色、苏木精染色、番红O-固绿染色、抗酒石酸酸性磷酸酶(tartrate-resistant acid phosphatase,TRAP)染色,分析大鼠TMJ髁突软骨的组织病理学变化。结果形态学观察显示1周组模型侧关节盘红肿明显,4周组模型侧可见典型的骨关节病鸟嘴样改变,1周组和4周组模型侧髁突的高度[分别为(2.73±0.14)和(2.49±0.25)cm]均显著低于对照侧[分别为(3.30±0.09)和(3.30±0.12)cm](P<0.01);影像学结果显示4周组模型侧骨小梁微观结构破坏明显;番红O-固绿染色结果显示1周组及4周组模型侧的蛋白聚糖均显著低于对照侧(P<0.01);TRAP染色结果显示1周组及4周组模型侧的破骨细胞数目均显著多于对照侧(P<0.01);免疫组织化学染色、苏木精染色结果显示1周组及4周组模型侧的胶原纤维密度较对照侧均显著减少(P<0.01),而基质金属蛋白酶显著增多(P<0.01)。结论大鼠关节盘穿孔后,模型侧髁突软骨出现了典型的TMJOA病理改变。     

颞下颌关节骨关节病中蛋白多糖的组织化学研究

目的研究颞下颌关节骨关节病中蛋白多糖各组分的变化并探讨其与骨关节病的关系。方法18只新西兰白兔用颞下颌关节上腔内注射3%基质金属蛋白酶-10.1ml的方法,建立颞下颌关节骨关节病的动物模型。于术后24h、1周、2周、4周、8周、12周各处死3只兔,切取颞下颌关节标本,行苏木精-伊红和酸性黏多糖的阿新蓝(Alcianblue)染色法。在光镜下观察髁突软骨蛋白多糖(PGs)中糖胺聚糖(GAG)、透明质酸(HA)在骨关节病不同时期的变化。结果注药后1周阿新蓝染液pH1.0染色见髁突软骨中GAG染色变浅;第2周GAG染色较1周时稍深,阿新蓝染液pH2.5染色见髁突软骨中HA染色变浅;第4周GAG染色不均,整体变淡,HA含量明显减少,仅见钙化软骨层散在蓝染;第8周髁突软骨全层GAG染色极淡。各层染色无明显差别。HA在髁突软骨几乎无染色;第12周GAG染色总体极淡,HA无染色。结论蛋白多糖量和化学结构的变化是颞下颌关节骨关节病变发展过程中一个重要的特征,蛋白多糖随颞下颌关节骨关节病的发展逐渐丧失,与骨关节的病变呈正相关。     

血管内皮生长因子在颞下颌关节软骨细胞中的表达

目的：探讨血管内皮生长因子（vascular endothelial growth factor,VEGF）在颞下颌关节髁突软骨改建过程中的作用。方法：采用新西兰大耳白兔30只,分为术后24h和1、3、5、8周5个时间组及1个对照组,每组5只,用打击装置造成动物单侧下颌骨骨折,行钛合金小夹板坚强内固定,按时间分组处死动物取双侧颞下颌关节标本,观察髁突和关节盘软骨的组织学变化,应用免疫组化和原位杂交方法检测髁突软骨细胞内血管内皮生长因子及其受体Flt-1的表达,应用计算机图像分析系统计算阳性染色的灰度积分,应用SPSS10.0软件包进行配对q检验。结果：下颌外伤后双侧颞下颌关节髁突和关节盘均有不同程度损伤,髁突软骨增殖层和肥大层细胞胞质中检测到血管内皮生长因子及其受体Flt-1的表达,表达阳性强度随愈合时间而变化,各组阳性染色的灰度积分值差异具有统计学意义（P〈0.01）。结论：血管内皮生长因子及其受体Flt-1对颞下颌关节髁突损伤的修复起重要的生物学作用。     

咬合垂直距离降低对大鼠髁突软骨和软骨下骨形态学影响的初步研究

目的:探讨咬合垂直距离降低对大鼠颞下颌关节髁突软骨和软骨下骨改变的影响。方法:40只10周龄雄性大鼠随机等分为实验组和操作对照组。实验组通过降低大鼠牙冠高度的方法建立咬合垂直距离降低的动物模型,分别于处理后3、10、20、30d处死取材。30d组大鼠于实验处理前1d、处理后10、30d进行MICRO-CT扫描观察大鼠髁突软骨下骨形态改变。双侧颞下颌关节石蜡包埋、切片,通过HE染色观察大鼠髁突软骨形态学的改变。结果:①实验3d组与10d组髁突软骨中部厚度较操作对照组明显增厚(P<0.05),但实验20d组和30d组软骨中部厚度与操作对照组之间无显著差异(P>0.05)。所有实验组髁突软骨后部厚度在各时间点均较操作对照组显著增厚(P<0.05);②实验3d组髁突软骨增殖层出现了较大面积的胞核固缩,实验10d组部分关节(4/10)髁突软骨中出现了均质样无细胞区域,实验20d组与30d组髁突软骨各层形态基本与对照组相似;③实验30d组于10d时可见髁突软骨下骨后部出现骨质吸收凹陷,实验30d时凹陷变浅,骨表面又趋于光滑流畅。结论:①咬合垂直距离降低可以引起大鼠髁突软骨中后部的适应性改建;②实验早期改建活动较活跃,晚期改建活动趋于稳定。     

输送盘牵张成骨重建下颌髁突的骨密度和力学性能变化

目的 探讨运用输送盘牵张成骨术重建髁突的骨密度和力学性能变化.方法 成年山羊16只.截除右侧髁突后运用输送盘牵张成骨术重建髁突,左侧作为正常对照组.牵张结束后24周处死所有动物.采用双能X线吸收法和压缩力学性能测试技术.定量分析并对比两侧髁突的骨密度和压缩力学性能变化.结果 手术侧髁突骨密度较正常侧显著升高;其轴向弹性模量和最大应力较正常侧显著升高,横向弹性模量和最大应力两侧无显著性差异,轴向和横向最大应变两侧均无显著性差异.髁突骨松质的力学性能具有明显的各向异性.结论 运用输送盘牵张成骨术重建的髁突的骨密度和生物力学性能明显升高;这种适应性改建与颞下颌关节的功能刺激直接相关.     

Microscopic changes in the condyle and disc in response to distraction osteogenesis of the minipig mandible.

PURPOSE: Unilateral mandibular distraction osteogenesis (DO) has been shown to cause gross changes in the mandibular condyle and articular disc. The purpose of this study was to correlate histologic findings with these gross changes in a minipig distraction model. MATERIALS AND METHODS: Semiburied distractors were placed via submandibular incisions in 15 minipigs. Two unoperated animals served as controls. The protocol consisted of 0-day latency and rates of 1, 2, or 4 mm/day for a 12-mm gap. After the minipigs were killed (at 0, 24, or 90 days), ipsilateral and contralateral condyles and discs were harvested, decalcified, prepared for standard paraffin embedding, and evaluated to determine changes in 1) morphology and thickness of the articular cartilage and subchondral bone and 2) morphology of the disc. RESULTS: In control animals, there were no degenerative changes in the articular cartilage and underlying condylar bone; there were no significant differences in the mean articular cartilage thickness. The temporomandibular joint discs were normal. In experimental animals, distracted condyles showed increasing degenerative changes and mean articular cartilage thickness as the DO rate increased. The discs were thinner. These changes were present, but to a lesser degree, in the contralateral condyles. After 90 days, degenerative changes in the condyles and discs were reduced, after remodeling, except in the 4 mm/day DO group. CONCLUSIONS: Histologic changes in the condyles and temporomandibular joint discs in response to mandibular DO correlated with previously reported gross changes. These changes were greater at higher distraction rates and remodeling back to normal occurred in mandibular condyles distracted at 1 mm/day.     

Reconstruction of mandibular condyle by transport distraction osteogenesis: Experimental study in rhesus monkey.

PURPOSE: This study investigated histomorphologic changes in the newly formed condyle reconstructed by transport distraction osteogenesis through a nonhuman primate model. MATERIALS AND METHODS: Six adult rhesus monkeys were used in this study. Bilateral condyles and articular discs were extirpated, and the technique of transport distraction osteogenesis was carried out to reconstruct the condyles. X-ray and 3-dimensional (3D) computed tomography (CT) scanning films were taken at various intervals. Two monkeys were killed respectively at 4, 12, and 24 weeks after completion of distraction; the transport segments and the distracted calluses were harvested and processed for histologic examination. The original condyles removed at surgery served as normal control. RESULTS: Open bite was seen in all animals postoperatively and diminished at the end of distraction. Bone regeneration was perfect in the distraction gap between the transport disc and the pre-existing mandible. The bony transport disc gradually remodeled to a neocondyle that was similar to the original condyle in the appearances and structures. The head of neocondyle was covered with a fibrous cap, which might play the role of an articular disc. CONCLUSION: A neocondyle with functional shape can be created by transport distraction osteogenesis. This suggests that this technique is an alternative method for reconstruction of the mandibular condyle.     

Histological evaluation of condylar hyperplasia model of rabbit following distraction osteogenesis of the condylar neck

Summary Condylar hyperplasia is the excessive unilateral growth of mandibular leading to facial asymmetry, occlusal disturbance, joint pain and dysfunction. The aim of this study is to evaluate the histological presence of temporomandibular joint in model of condylar hyperplasia by lengthening unilateral condylar neck of distraction osteogenesis. An extra oral distractor was employed to achieve unilateral condylar neck distraction (1·0 mm daily for 7 days). The experimental condylar necks were elongated by 7 mm compared to the contralateral. Eleven adult white rabbits were used. Eight rabbits were, respectively, sacrificed after the post‐distraction period (4 or 8 weeks). All animals were evaluated clinically and histomorphometrically. The condyles radiologically showed remodelling, flattening and sclerosis. In 4‐week group, thinning of the cartilage was evident, and the trabeculae were long, not multiply connected. A thin, dense fibrous layer covered all over the surface of cartilage. In 8‐week group, the cartilaginous layer was similar to thickness of the normal cartilage, but still thinner than control. However, the fibrous layers covering condyle manifested slight degenerative changes, and even depressions and erosions were seen in the cartilage and subchondral bone. The trabeculae showed denser and multiply connected. In 8‐week group, the cartilaginous thickness of surgical condyles was significantly thinner than the contralateral. This study indicates that unilateral distraction of condylar neck loads the condyles asymmetrically. Asymmetrical loads affect more on the surgical condyles than the contralateral, and after 8 weeks of the post‐distraction, condyle could recover from asymmetrical loads in some degree.     

牵引成骨结合组织工程化软骨重建山羊髁突缺损的实验研究

目的：利用牵引成骨结合组织工程化软骨重建山羊髁突缺损。方法：12只山羊随机分为两组：实验组在下颌切迹下方作截骨线,切除一侧髁突及其颈部,左右随机。再于下颌支后缘形成转移盘,在转移盘的远中植入软骨细胞支架复合物。对照组在转移盘的远中仅植入支架。分别于牵引结束4、8、12周大体及组织学观察山羊髁突的形成情况。结果：牵引结束后4周,实验组山羊髁突已具备良好的外形,髁突表面覆盖软骨组织：对照组山羊新形成之髁突外形虽与正常髁突相似但表面无软骨层。12周时,实验组山羊髁突外形与正常髁突相似,表面仍有软骨层覆盖：而对照组山羊新形成的髁突外形虽与正常髁突相似,但表面仍无软骨层覆盖。结论：利用牵引成骨结合组织工程化软骨的方法不仅可以从外形上重建山羊髁突,而且在解剖结构上与正常髁突相似,为髁突正常功能的行使提供了良好的解剖学基础。     

Changes in the temporomandibular joint after mandibular lengthening with different rates of distraction

This study assessed the changes in the condyle after mandibular lengthening with 2 different rates of distraction (1 mm/day and 2 mm/day). Unilateral mandibular distraction was performed in 8 young adult goats. The animals were sacrificed 8 weeks after the completion of distraction, and the temporomandibular joint (TMJ) specimens were harvested and processed for histologic examination and histomorphometric analysis. Adaptive changes in the condyle were observed in the goats distracted at a rate of 1 mm/day, whereas degenerative alterations were found in those distracted at a rate of 2 mm/day. This study suggests that the TMJ is able to withstand the impact of distraction at a rate of 1 mm/day, but more rapid distraction may induce degeneration in the condylar cartilage.     

运用输送盘牵张成骨术重建猴下颌髁突的实验研究

目的研究在猴颞下颌关节（TMJ）缺损动物模型上运用输送盘牵张成骨术重建髁突的可行性及其整复效果。方法选取6只成年恒河猴,手术截除其双侧关节髁突与关节盘,在下颌升支部行“L”形骨切开术,形成骨输送盘,并安置自行研制的牵张器。按每次0.4 mm,每次间隔12 h的牵张速率向上牵引输送盘至关节窝。牵张结束后第4、12、24周各处死2只动物。通过影像学分析和组织学检查评价输送盘改建与牵张间隙内新骨生成情况。以术中切除的髁突作为正常对照组。结果术后所有动物都有不同程度的咬合错乱,牵张结束后咬合基本恢复正常。骨输送盘形态基本接近正常髁突,其下方可见大量软骨细胞;牵张间隙内新骨生成良好。结论输送盘牵张成骨术可以重建一个形态和功能都基本接近正常的髁突,这种技术可以作为一种整复TMJ缺损的新方法。     

Micro-computed tomography evaluation of the glenoid fossa and mandibular condyle bone after bilateral vertical ramus mandibular distraction in a canine model

The aim of this study was to quantify bone microarchitecture within the glenoid fossa and mandibular condyle following mandibular distraction osteogenesis. Eight 6- to 9-month-old male beagle dogs underwent bilateral vertical mandibular distraction with semiburied distractors (12 days of distraction at 1 mm per day). One unoperated animal served as control. After distraction the animals were divided into two groups (N = 4) and killed after 1 or 2 months of consolidation. Three-dimensional trabecular architecture was analyzed by micro-computed tomography (muCT). At both sites the overall trends were similar. In the glenoid fossa, there was decreased bone volume, trabecular number, and connectivity density and increased trabecular separation at 1 month and decreased trabecular thickness and increased structure model index compared with the control (P < 0.05). In the mandibular condyle, there was decreased bone volume, trabecular number, and connectivity density at both 1 and 2 months, with decreased trabecular thickness and increased structure model index at 2 months only compared with the control (P < 0.05). The bone became less dense and more rodlike. These bone changes are similar to those seen by the effects of aging or impaired normal function. Thus, in the short term, changes occur in the bone microstructure of the glenoid fossa and mandibular condyle after vertical mandibular ramus distraction in the canine model.     

Micro-computed tomography evaluation of the glenoid fossa and mandibular condyle bone after bilateral vertical ramus mandibular distraction in a canine model

The aim of this study was to quantify bone microarchitecture within the glenoid fossa and mandibular condyle following mandibular distraction osteogenesis. Eight 6- to 9-month-old male beagle dogs underwent bilateral vertical mandibular distraction with semiburied distractors (12 days of distraction at 1 mm per day). One unoperated animal served as control. After distraction the animals were divided into two groups (N = 4) and killed after 1 or 2 months of consolidation. Three-dimensional trabecular architecture was analyzed by micro-computed tomography (microCT). At both sites the overall trends were similar. In the glenoid fossa, there was decreased bone volume, trabecular number, and connectivity density and increased trabecular separation at 1 month and decreased trabecular thickness and increased structure model index compared with the control (P < 0.05). In the mandibular condyle, there was decreased bone volume, trabecular number, and connectivity density at both 1 and 2 months, with decreased trabecular thickness and increased structure model index at 2 months only compared with the control (P < 0.05). The bone became less dense and more rodlike. These bone changes are similar to those seen by the effects of aging or impaired normal function. Thus, in the short term, changes occur in the bone microstructure of the glenoid fossa and mandibular condyle after vertical mandibular ramus distraction in the canine model.