颈椎软骨终板钙化与颈椎间盘退变和椎体骨赘形成的关系

目的：研究颈椎软骨终板钙化与颈椎间盘退变和颈椎椎体骨赘形成的关系。方法：应用组织学方法观察颈前路环锯手术切下的18例脊髓型颈椎病和4例颈椎过伸性损伤致颈椎间盘突出患者的颈椎间盘及相邻的上下椎体标本,研究不同退变程度颈椎间盘软骨终板和椎间盘的形态学变化及椎体骨赘形成过程。结果：退变程度较轻或基本正常的颈椎间盘软骨终板结构良好,潮标清晰,退变程度较重的颈椎间盘软骨终板发生明显纤维化,潮标前移,钙化软骨和软骨下骨板增厚,退变颈椎间盘周边软骨终板潮标明显前移,钙化和骨化层增厚,形成突向外侧的椎体边缘的骨赘。结论：颈椎软骨终板的不断钙化和骨化导致颈椎间盘营养发生障碍可能是启动颈椎间盘退变的关键因素,退变椎体周边软骨终板的不断钙化和骨化是椎体骨赘形成的根本原因。     

退变椎体周边关节软骨产生碱性磷酸酶与骨赘形成的关系

目的：研究椎体骨赘形成的机理。方法：通过切除免颈棘上韧带及棘间和分离颈椎后旁两侧肌肉引起动物颈椎力学上的失衡,经３个月的时间的发展而造成免颈椎间盘退变模型。用生物化学方法分别测定每个动物颈椎间盘纤维环和髓核、椎体关系软骨、周边关节软碱性磷酸酶性结果：颈椎间盘退变动物椎体周边关节软骨中碱性磷酸酶活性明显升高。结论：研究结果在生物化学上支持椎体骨赘来自于周边关节软骨增殖、化生、钙化和骨化的组织学观察。     

Molecular basis of achondroplasia, hypochondroplasia, and thanatophoric dysplasia]

Fibroblast growth factor 2 (FGF2) inhibits proliferation and hypertrophy of chondrocytes in the growth plate, synthesis of cartilage matrix, terminal differentiation of hypertrophic chondrocytes and matrix calcification. Recent studies have found that mutations in the receptor for fibroblast growth factor 3 (FGFR3) cause achondroplasia, hypochondroplasia and thanatophoric dysplasia. These mutations evoke uncontrolled stimulation of the receptor, leading to inhibition of bone growth. Inactivation of the receptor in experimental animals causes excessive chondrocyte proliferation and abnormal bone length. Chondrocyte stem cells proliferate in the ossification groove of Ranvier and contribute to both peripheral and longitudinal growth of the growth plate. They express FGFR3, have a potential to differentiate into chondrocytes and are therefore considered adequate for healing cartilage defects in the articular surface. It is at present unknown what happens to the chondrocyte precursor cells in the ossification groove of patients with FGFR3 mutation.     

Effects of ethane-1-hydroxy-1,1-diphosphonate on ossification of the posterior longitudinal ligament in Zucker fatty rats

PURPOSE: Using Zucker fatty rats as an animal model, we evaluate the effectiveness of ethane-1-hydroxy-1,1-diphosphonate on ossification of the posterior longitudinal ligament by histopathologically investigating the prodromal, early, and advanced stages of ossification of the spinal ligaments. METHODS: 73 Zucker fatty rats were allocated to the ethane-1-hydroxy-1,1-diphosphonate group (n=33) and the control group (n=40). The former group was fed ethane-1-hydroxy-1,1-diphosphonate daily. The feed was given starting 2 months after birth and continued until the rats were killed at 3 to 18 months later. Chemical analysis of the blood, radiographic tests, and histopathological examination were then conducted for both groups. RESULTS: The results showed that ossification of the spinal ligaments involved excessive cartilage cell proliferation around areas affected by enthesitis; enlargement of the fibrocartilage tissue layer; ligament thickening; calcification of the matrix around the cartilage cells; and ossification of the spinal ligaments through enchondral ossification. Radiographic examinations showed that osteoproliferation in vertebral bodies in rats receiving ethane-1-hydroxy-1,1-diphosphonate was generally suppressed compared with controls, whereas histopathological examinations found no clear difference in cartilage cell proliferation in areas affected by enthesitis between the two groups, indicating the absence of calcification or osteo-proliferation in areas affected by enthesitis for the rats receiving ethane-1-hydroxy-1,1-diphosphonate. CONCLUSION: Ethane-1-hydroxy-1,1-diphosphonate is effective in suppressing progressive ligament ossification.     

软骨终板钙化在椎间盘退变过程中的作用机理

目的：研究椎体软骨终板钙化在椎间盘退变过程中的作用。人新西兰兔随机分为造模与对照组２组,每组发３个月和８个月２个观察亚组。切作造模组动物颈棘上、棘间韧带及分离颈椎后旁两侧肌肉,造成颈椎力学上的失衡而诱导兔颈椎间盘退行性改变。在术后３个月和８个地分别处死,取颈椎间盘组织,行病理学检查在形态学上评定颈椎间盘退变程度,测定不同退变程度椎间盘软骨终板钙化层厚度。结果：退变程度较轻或基本正常的颈椎间盘,软骨     

异体软骨细胞复合Pluronic修复关节软骨缺损

目的 探讨运用同种异体软骨细胞复合Pluronic修复关节软骨缺损的可行性，并应用^3H—TdR放射自显影方法鉴别软骨缺损修复的细胞来源。方法 取同种异体软骨细胞体外培养至第2代，用^3H—TdR标记后复合Pluronic植入兔关节软骨缺损区作为实验组，并采用单纯Pluronic植入作为材料对照组，不作任何处理组为空白对照组，分别于4、8及16周取材，观察其修复效果，并应用放射自显影方法鉴别修复组织的细胞来源。结果 实验组术后8周，缺损表面可见新生软骨形成，术后16周缺损完全修复，表面光滑，与周围界限模糊，放射自显影证实所修复组织的细胞来源于植入细胞。材料对照组及空白对照组缺损均未见明显修复。结论 ①同种异体软骨细胞复合Pluronic修复关节软骨缺损是可行的；②^3H—TdR标记细胞可作为鉴别细胞来源的一种简便可行的方法。     

不同年龄兔前交叉韧带切断后关节软骨变化的研究

目的探讨膝关节前交叉韧带（anterior cruciate ligament,ACL）切断对不同年龄兔关节软骨的影响,为临床选择方法和时机处理不同年龄ACL损伤的病人提供实验依据。方法健康新西兰大白兔30只,按照年龄分成6、12、24个月组,每组10只。每组再随机分为5个小组。切断右膝关节ACL,左膝仅行切开术作为自身对照。分别于术后5、10、15、20、25周气栓处死实验动物,大体观察并对股骨关节软骨进行损伤评分,对股骨内髁进行Masson染色并显微镜观察,测定软骨含水率。结果大体观察和Masson染色病理切片显示,12月龄组兔软骨损伤发展最快,24月龄组兔发展最慢。术后25周时12月龄组兔软骨损伤最重,6月龄组兔次之,24月龄组兔软骨损伤最轻。随着软骨损伤的发展,右侧ACL切断（阳性对照侧）软骨含水率呈现出先升高后降低的趋势。结论不同年龄兔ACL断裂后软骨损伤存在差异,提示ACL断裂后软骨的损伤与年龄有紧密的关系。     

Relation of coxarthrosis to stresses and morphogenesis: A finite element analysis

We calculated subchondral deformations and stresses in the femoral head and acetabulum during weight bearing using finite element models. Areas of high joint contact pressures on the femoral head were shown to correspond to high hydrostatic compression in subchondral bone. The magnitude of the subchondral bone compressive hydrostatic stress correlated with cartilage thickness and was highest in the superior femoral head and moderate at the acetabular roof. The seldom contacting surfaces of the medial-inferior and peripheral areas of the femoral head and the roof of the acetabulum had lower hydrostatic compression and significant subchondral bone tensile strains tangential to the joint surface. Initial cartilage fibrillation and osteophyte formation are often found in these areas. These findings suggest that fluctuating hydrostatic pressure inhibits vascular invasion and the degeneration and ossification of articular cartilage. The generation of tensile strain may promote the degenerative process by direct mechanical mechanisms. Additionally, since tensile strains are associated with a reduction in the compressive hydrostatic stresses in the cartilage and an increase in shear stresses, their presence may permit or promote vascular invasion, cartilage degeneration, and osteophyte formation. These mechanical principles in arthrosis are the same as those that have been previously demonstrated to guide the degeneration and ossification of the cartilage primordium during skeletal morphogenesis. In this sense, arthrosis may be viewed as the final stage in the degeneration and ossification of the cartilage anlage.     

Relation of coxarthrosis to stresses and morphogenesis. A finite element analysis

We calculated subchondral deformations and stresses in the femoral head and acetabulum during weight bearing using finite element models. Areas of high joint contact pressures on the femoral head were shown to correspond to high hydrostatic compression in subchondral bone. The magnitude of the subchondral bone compressive hydrostatic stress correlated with cartilage thickness and was highest in the superior femoral head and moderate at the acetabular roof. The seldom contacting surfaces of the medial-inferior and peripheral areas of the femoral head and the roof of the acetabulum had lower hydrostatic compression and significant subchondral bone tensile strains tangential to the joint surface. Initial cartilage fibrillation and osteophyte formation are often found in these areas. These findings suggest that fluctuating hydrostatic pressure inhibits vascular invasion and the degeneration and ossification of articular cartilage. The generation of tensile strain may promote the degenerative process by direct mechanical mechanisms. Additionally, since tensile strains are associated with a reduction in the compressive hydrostatic stresses in the cartilage and an increase in shear stresses, their presence may permit or promote vascular invasion, cartilage degeneration, and osteophyte formation. These mechanical principles in arthrosis are the same as those that have been previously demonstrated to guide the degeneration and ossification of the cartilage primordium during skeletal morphogenesis. In this sense, arthrosis may be viewed as the final stage in the degeneration and ossification of the cartilage anlage.     

Reconstruction of Articular Cartilage with Free Autologous Perichondrial Grafts

An experimental study in adult rabbits has been performed to find out whether the cartilage forming capacity of the perichondrium could be utilized in reconstruction of articular cartilage. The normal articular cartilage of the glenoid surface of the humero-scapular joint was completely removed. Auricular perichondrium was grafted to cover the exposed bony surface with the active chondrogenic layer of the perichondrial graft facing the joint cavity. The joint was not immobilized but the operated limb was amputated at wrist level to avoid weight bearing. The animals were sacrificed at different time intervals ranging from 1 to 17 weeks. In 12 out of 14 grafted rabbits regeneration of cartilage occurred. In 6 of 10 control cases where no perichondrium was grafted to cover the resected surface no cartilage was found. In the other 4, only small areas of mature cartilage were seen, probably remnants of the original articular cartilage.     

新鲜同种异体骨软骨移植修复软骨缺损

目的联合应用新鲜同种异体骨软骨移植,和局部注射碱性成纤维细胞生长因子(basic fibroblast growthfactor,bFGF),探讨能否促进关节软骨缺损区新生软骨的形成,提高软骨缺损修复的成功率。方法48只青紫兰兔,96个实验关节,随机分为A、B、C、D组。无菌条件下制作骨软骨缺损模型。在A组缺损区单纯植入新鲜的同种异体骨软骨,B组单纯局部注射重组人bFGF,C组局部注射bFGF后同时植入新鲜的同种异体骨软骨,D组用作空白对照。术后第4、8、12周作大体观察、X线摄片、组织学检查及免疫组化检查。结果移植加注射bFGF组促进软骨缺损修复的效果均好于其他组,图像分析仪进行软骨细胞记数有显著差异(P<0.05),有统计学意义。修复软骨型胶原免疫组化染色强阳性。结论采用新鲜的同种异体骨软骨移植及联合应用碱性成纤维细胞生长因子,二者能起交互作用,促进了新生软骨的形成。     

软骨终板钙化与椎间盘退变关系的实验研究

目的　研究椎体软骨终板钙化与椎间盘退变的关系。　方法　通过切除２０ 只兔颈椎棘上、棘间韧带及分离颈椎后旁两侧肌肉造成颈椎力学上的失稳而诱导了颈椎间盘退变动物模型。在形态学上评定颈椎间盘退变程度,测定不同退变程度椎间盘软骨终板钙化层与非钙化层厚度。　结果　软骨终板钙化层厚度与椎间盘退变程度呈高度正相关性（ｒ＝ ０－９２） 。　结论　软骨终板的钙化可能是椎间盘退变的启动和促进因素     

Computer model of endochondral growth and ossification in long bones: biological and mechanobiological influences.

Endochondral growth and ossification, the processes by which cartilage increases in size and is replaced by bone, are affected by biological factors such as intrinsic genetic makeup and systemic chemical agents. In addition, these processes are affected by epigenetic mechanical factors: they may be accelerated in regions of intermittent high shear stress and decelerated in regions of intermittent high hydrostatic pressure. Previous models of bone development have not incorporated both biological and mechanobiological influences on endochondral growth and ossification. We have implemented a finite element analysis to model a developing bone rudiment from 8 weeks of gestational development to approximately 2 years after birth. As a function of time, we calculated a maturity index that reflects the progression of a region of cartilage through the endochondral ossification sequence of proliferation, hypertrophy, mineralization, and replacement by bone. We calculated a specific growth rate for each region of cartilage and estimated overall longitudinal growth of the rudiment. Regions of cartilage replaced by bone were remodeled. The results from the maturity index can be compared with distributions of proliferative, hypertrophic, and mineralized cartilage seen on histology at various stages in development. The results of the simulation predicted prenatal and postnatal developmental events, including formation of a secondary ossific nucleus, a layer of articular cartilage, and a growth plate. Our results demonstrate the necessity to include biological and mechanobiological influences when endochondral growth and ossification are considered.     

Osteoarthritis of the Knee in the Rabbit Produced by Immobilization:: Attempts to Achieve a Reproducible Model for Studies on Pathogenesis and Therapy

In order to obtain a reproducible experimental model of osteoarthritis a method of immobilizing the rabbit's knee in extension by means of a plastic splint was developed. The right knees of the rabbits were immobilized for periods varying from 4 days to 24 weeks. With the left knees as controls the knees were studied in a variety of ways among these being radiography (126 rabbits), histological sections stained with Alcian Blue (88 rabbits), analysis of ³⁵S-sulphate uptake (22 rabbits) and ³⁵S-autoradiography (6 rabbits). In 27 rabbits the regaining of mobility after immobilization was studied. After 5-6 weeks of immobilization most of the knees showed moderate or severe changes including loss of articular cartilage and osteophyte formation. Immobilization of the rabbit's knee by this method provokes a fairly easily reproducible type of degenerative joint disease showing similarities to advanced osteoarthritis as seen in humans.     

Reconstruction of patellar cartilage defects with free periosteal grafts. An experimental study

The osteo-chondrogenic potential of free periosteal grafts was investigated within the knee joint in 26 rabbits aged four to six weeks. A total of 36 knee joints were operated on. The grafts were stripped from the medial side of the right tibia and sutured on the articular surface of the patella, from which the cartilage had been totally excised to the subchondral bone. In 16 knees the graft was sutured with the cambium layer towards the subchondral bone and in eight knees the fibrous layer faced the bone. In the control group of twelve knees the patellar articular cartilages were excised and no periosteal transplant was grafted to the patellar articular surface. In the transplantation group cartilage formation could be seen already one week after the operation. There were no marked differences between the series with the cambium layer facing the subchondral bone or the group with the fibrous layer facing the bone. At 20 weeks the hypertrophied cartilage had thinned and resembled normal joint cartilage. In the control group the histological picture resembled osteoarthritis.     

Scattered Mitosis in Adult Joint Cartilage after Partial Chondrectomy: A Histological,Autoradiographical and Biochemical Study in Rabbits

Full-grown rabbits were operated on and subjected to total or partial chondrectomy of the cartilage in the patellar groove. In one group, only arthrotomy was performed in the control knee. The animals were killed at various times after the operation. Histologically, proliferation of the synovial cells at the joint margins, as well as osteoblastic activity, could be seen; later, osteophyte formation was observed. There were only minimal signs of degenerative changes in the cartilage. The biochemical investigation did not show any difference in the nucleic acids of the cartilage. either in relation to the time after the operation had taken place or in relation to the size of the trauma. In the knees where the cartilage was excised, thymidine-labelled chondrocytes were seen scattered in the joint. The number of labelled chondrocytes showed a rising tendency up to 14 days postoperatively, but no peak value was seen. In the arthrotomized knee joints, labelled chondrocytes were occasionally seen. It is possible that the scattered mitosis is the result of a reduction in the concentration of normal cell-specific inhibitors of mitosis, so-called chalones.     

关节软骨-骨一体化修复体修复全层关节软骨缺损的实验研究

目的 评价新型多级结构仿生型关节软骨-骨一体化修复体的生物相容性,使用一体化修复体对兔关节全层软骨缺损进行修复,并对修复结果进行组织形态学观察.方法 1.生物相容性实验:包括急性毒性实验、溶血实验、免疫原性实验及慢性毒性实验.2.关节软骨修复实验:制作全层关节软骨缺损动物模型,随机于一侧植入一体化修复体,另一侧不予处理.术后4、6、8和12周分别处死动物,取修复组织行大体、放射学、组织学观察并用Wakitani法进行组织形态学评分.结果 1.生物相容性实验:(1)急性全身毒性实验动物体质量呈上升趋势,且各组体质量增加比较无显著性差异.(2)3种浓度梯度的修复材料溶血率均未超过5%.(3)慢性毒性实验:术后12周动物肝肾功能与正常对照组及术前比较无显著性差异.2.关节软骨修复实验:术后4～8周植入侧修复组织主要为透明软骨,表面光整平滑有光泽,与周围组织整合良好,对照侧无明显修复组织.Wakitani评分各组间差异均有统计学意义,实验组明显优于对照组.结论 多级结构仿生型关节软骨-骨一体化修复体具有良好的生物相容性,并且在动物体内可诱导全层关节软骨缺损后的修复.

Abstract：

Objective To observe the biocompatibility of a biomimetic designing of a multi-grade compositions in repairing articular cartilage and subchondral bone in animal bodies and repair the fullthickness defects in articular cartilage with the compositions and to study the regenerated cartilage histomorphologically. Methods Biocompatibility study: Acute general toxicity test, Haemolysis test, subcutaneous implantation test and chronic toxicity test. Articular cartilage defects repaired experimental study :The models of defects in articular cartilage were made artificially in both condylus lateralis femoris of mature rabbits. Implanted with the biomimetic designing of a multi grade compositions randomly at one side as the experimental group and the other side were untreated as the control group. The rabbits were killed at 4, 6, 8and 12 weeks after operation, respectively, with 6 ones at each time, and the macroscopic, histological, ultrastroctural examinations and semi-quantity cartilage scoring employing Wakitanifa repaired cartilage value system were performed. Results Biocompatibility study: (1) The rabbits' weight in experimental group kept growing .(2) Haemolysis rate of rats to different concentrations of diffusion solution was＜5%.(3) In chronic toxic reaction, rabbits' liver and kidney function was not different compared with the control groups at 12weeks and the index before operation. Articular cartilage defects repaired experimental study: 4-8 weeks after operation, the defects in the experimental group were partly filled with hyaline cartilage. Twelve weeks after operation, the defects in the experimental group were completely filled with mature hyaline cartilage.However, fibrous tissues were seen in the control group all the time. At 4, 6, 8, and 12 weeks postoperatively, the Wakitanifa cartilage scores were (7.60±0.98), (5.69±0.58), (4.46±0.85) and (4.35±0.12), respectively,in the experimental group and (10.25±1.05), (9.04±0.96), (8.96±0.88) and (8.88±0.68), respectively, in the control group. Differences between the control group and the experimental group were significant. Conclu sion The biomimetic designing of a multi-grade compositions has good biocompatibility and may induce cartilage regeneration to repair the full-hickness defects of articular cartilage.     

Effects of low-intensity pulsed ultrasound in repairing injured articular cartilage

Articularcartilageisakindofavascularmusculoskeletaltissueswitharelativelylowcapacityforintrinsicrepairorregeneration.Intheabsenceofavailablestemcells,thereislittlehopeforcartilagerepairafterinjuryandthetissuesprogress alongadegenerativepathwaythatdestroysthe biochemicalandbiomechanicalproperties.Sorepairof damagedarticularcartilageisoneofthemostdifficult problemsinorthopaedicsandnosatisfactorytreatment methodhasbeenfoundinthisfield.Ultrasoundhas beenwidelyusedinclinicaldiagnosisandtreatment.It…     

Scattered Mitosis in Adult Joint Cartilage after Partial Chondrectomy: A Histological, Autoradiographical and Biochemical Study in Rabbits

Full-grown rabbits were operated on and subjected to total or partial chondrectomy of the cartilage in the patellar groove. In one group, only arthrotomy was performed in the control knee. The animals were killed at various times after the operation. Histologically, proliferation of the synovial cells at the joint margins, as well as osteoblastic activity, could be seen; later, osteophyte formation was observed. There were only minimal signs of degenerative changes in the cartilage. The biochemical investigation did not show any difference in the nucleic acids of the cartilage. either in relation to the time after the operation had taken place or in relation to the size of the trauma. In the knees where the cartilage was excised, thymidine-labelled chondrocytes were seen scattered in the joint. The number of labelled chondrocytes showed a rising tendency up to 14 days postoperatively, but no peak value was seen. In the arthrotomized knee joints, labelled chondrocytes were occasionally seen. It is possible that the scattered mitosis is the result of a reduction in the concentration of normal cell-specific inhibitors of mitosis, so-called chalones.     

The effects of hyaluronic acid on fibronectin fragment mediated cartilage chondrolysis in skeletally mature rabbits

OBJECTIVE: Intraarticular Na-Hyaluronate (HA) exerts a beneficial effect on adolescent rabbits after fibronectin fragment (Fn-f) mediated cartilage injury. We extended our studies to a population of rabbits which have reached full skeletal maturity. DESIGN: Adult male NZW rabbits received an injury with Fn-f and no further treatment; an injection of HA followed by Fn-f injury, or Fn-f injury followed by a single or weekly intraarticular injection of HA. All animals were sacrificed 38 days after receiving the Fn-f injury. After sacrifice, proteoglycan (PG) content was determined from articular cartilage from the medial femoral condyles and tibial plateaus. The patellae were processed for histology. RESULTS: Cartilage PG contents were significantly reduced after Fn-f injection (P=0.0167) and were only slightly improved with HA pre-treatment. However, post-treatment with HA resulted in significant improvements in cartilage PG content when compared to Fn-f only (single HA, P=0.01; weekly HA,P =0.01). Loss of Safranin-O staining, cell loss, osteophyte formation and inflammation were present in the patellae following Fn-f injection. Pre-treatment with HA reduced these changes. More significant protection of cartilage and restoration of Fn-f injury were noted in animals receiving post-treatment with HA. CONCLUSIONS: These results suggest that 38 days after Fn-f injury the lost PG content induced by Fn-f injection is substantially restored by weekly post-treatment with intraarticular HA in rabbits that have reached full skeletal maturity.