Subchondral route for nutrition to articular cartilage in the rabbit. Measurement of diffusion with hydrogen gas in vivo.

The route of nutrients going to articular cartilage was studied by determining the diffusion of hydrogen molecules from the subchondral circulation to the articular cartilage in rabbits. In all immature animals there was diffusion of hydrogen from subchondral bone into articular cartilage, while in the older immature animals the results were variable. None of the mature animals showed any diffusion of hydrogen into articular cartilage. The rate of diffusion of hydrogen was significantly lower in the articular cartilage than in the subchondral bone in the immature animals while the concentrations of hydrogen in the articular cartilage were only fractions of those in the subchondral bone at the same instant. Histologically, the deep layers of immature cartilage are penetrated extensively by vascular buds from the ossified portion of the epiphysis, while in adults the articular cartilage is separated from subchondral vascular spaces by an end-plate of bone. Blood vessels penetrating into the basilar layer of articular cartilage in immature animals appear to play an important role in the nutrition of articular cartilage coming from the subchondral region.     

正常膝关节软骨钙化层形态结构研究

目的探索关节软骨钙化层的结构形态及其与软骨非钙化层和软骨下骨之间的界面连接方式。方法组织库获取自愿捐献的人体正常股骨髁新鲜标本20个,男10个,女10个;年龄17～45岁。常规制备石蜡横、纵切片,番红O／固绿和冯库萨染色观察钙化层形态结构;扫描电镜观察软骨各层之间的界面连接方式;连续切片结合建模技术建立骨软骨三维模型。结果关节骨软骨复合组织番红O／固绿染色结果示软骨红染,软骨下骨蓝染,钙化层位于潮线与黏合线之间;冯库萨染色结果示钙化层黑染,结构及边界清晰,上界面以波浪状潮线结构与非钙化层紧密连接,下界面以凹凸不平的梳齿状结构与软骨下骨相互锚合：关节骨软骨剥离面及断面扫描电镜示钙化层与非钙化层以沟壑镶嵌方式相互嵌合;关节骨软骨复合组织纵切面观察,钙化层与软骨下骨间的黏合线呈凹凸不平的梳齿状结构;骨软骨三维模型观察结果与关节软骨自然剥离横断面扫描电镜观察结果基本一致。结论钙化层是关节软骨的重要结构,它通过特有界面连接方式将软骨牢牢固定在软骨下骨上。     

Restoration of arthritic cartilage defects using autologous chondrocytes transplantation is superior to cartilage-paste graft in rabbits

This study compared the articular cartilage repair potential of cultured chondrocytes transplantation with bone-cartilage paste-graft in the resurfacing of full-thickness defects without breaching of the subchondral bone plate in rabbit knees. A 5 x 5-mm articular cartilage defect was created in the patellar groove of the femur. Three months following creation, the defect was filled with cultured autologous chondrocytes (group 1) or bone-cartilage paste (group 2). A control group of untreated defects was followed for 1 year. The reparative tissue was analyzed macroscopically, histologically, and by immunohistochemistry 3-12 months post-transplantation. The surfaces of the reparative tissue in group 1 were smooth, and the defects were filled with reparative tissue that resembled hyaline cartilage. The composition of the repair tissue more closely resembled cartilage, as demonstrated by cartilage-specific stains. In contrast, the reparative tissue in group 2 was fibrous and exhibited markers of mesenchymal stem cells and bone formation. Transplantation of cultured chondrocytes into a full-thickness defect in the rabbit generates a biologic substitute tissue that resembles native articular cartilage with living cells capable of synthesizing the surrounding cartilage matrix. In contrast, analysis of the healing response to the paste-graft technique failed to show cartilage-like characteristics. This information may be clinically applicable to direct the use of these treatments in chondral injuries.     

Magnetic resonance imaging of periarticular titanium screws

Magnetic resonance imaging (MRI) may be the most sensitive modality for detecting post-traumatic degeneration of articular cartilage. Magnetic resonance imaging must accurately depict articular cartilage in the presence of periarticular fracture stabilization devices to be effective for postoperative imaging of articular fractures. This study examines how close titanium screws can be inserted to tibial articular surfaces and still allow accurate MRI of the overlying articular cartilage. Cannulated titanium screws were inserted at varying distances from subchondral bone in the proximal and distal tibiae of embalmed human cadaveric legs, which were then imaged using a standard nonfat-saturated fast low angle shot two-dimensional sequence (FLASH 2D). The distance from the center of the screw to the subchondral bone and the thickness of the articular cartilage directly overlying the screw was then determined by direct measurement and by measurement on the scanned images. To allow FLASH 2D MRI of the articular cartilage, 7.3-mm screws had to be at least 13 mm from the subchondral bone, and 4.5-mm screws had to be at least 12 mm from the subchondral bone. For MRI to be effective for the postoperative imaging of the articular surface following severe articular fractures of the tibia, titanium fracture hardware must be farther away from the articular surface than these minimum distances. Alternate materials for stabilizing articular fractures are available and may allow clearer and more accurate imaging of the articular cartilage when inserted close to the articular surface.     

Elastic modulus of calcified cartilage is an order of magnitude less than that of subchondral bone

The elastic moduli of calcified cartilage and subchondral bone tissues were measured experimentally with use of a three-point bending test. Specimens were obtained from a bovine patella and the distal end of a bovine femur, from two different animals. Fifteen specimens were tested as “pure” subchondral bone beams, and 15 were tested as composite calcified cartilage/subchondral bone beams. A least-squares optimization scheme was used to obtain modulus values from the composite beams. The elastic modulus for subchondral bone calculated from the “pure” subchondral bone beams was 2.3 ± 1.5 GPa (3.9 ± 1.5 GPa for specimens from the femur and 1.6 ± 0.7 GPa for specimens from the patella). The composite beam optimization resulted in a modulus for subchondral bone of 5.7 ± 1.9 GPa and a modulus for calcified cartilage of 0.32 ± 0.25 GPa. The modulus for the calcified cartilage was more than an order of magnitude lower than the modulus of the underlying subchondral bone. This supports the idea that the zone of calcified cartilage forms a transitional zone of intermediate stiffness between the articular cartilage and the subchondral bone.     

Quantitative ultrasound imaging of spontaneous repair of porcine cartilage

OBJECTIVE: Arthroscopy offers qualitative means to evaluate the surface of articular cartilage. However, possible degeneration of the deep cartilage and subchondral bone remains undetected. High frequency ultrasound imaging is an advanced cartilage evaluation method which is conceivable to arthroscopic use and brings diagnostic information also from deeper cartilage and subchondral bone. DESIGN: In this study, we characterized spontaneous repair of porcine cartilage in situ with quantitative 2D-ultrasound imaging. At the age of 7-8 months, a cartilage lesion (diameter 6mm, not penetrating into subchondral bone) was created on the lateral facet of the right femoral trochlea (n=8). The animals were sacrificed 3 months after the surgery. The lesion site, adjacent cartilage and the corresponding control area at the contralateral (left) knee were imaged in situ with 20 MHz ultrasound. Ultrasound reflection coefficients were determined from the cartilage surface (R) and from the cartilage-bone interface (R(bone)). Microtopography of the articular surface was quantified by calculating ultrasound roughness index (URI) parameter from the ultrasonically determined surface profile. RESULTS: Lesion site was spontaneously filled with visually cartilage-like soft tissue with smooth surface. However, ultrasonic images and histological analyses revealed erosion of subchondral bone under the lesion site. Ultrasound reflection (R) at the surface of the spontaneously repaired tissue was significantly lower (-73.5+/-7.6%, P<0.05) than at the surface of intact cartilage. R(bone) was lowest at the lesion site. The surface roughness of spontaneously repaired cartilage was significantly higher than that of the intact tissue (44.0+/-26.0 microm vs 7.5+/-2.3 microm, P<0.05). CONCLUSIONS: Quantitative ultrasound parameters offered diagnostic information revealing impaired structural integrity of the spontaneously repaired porcine cartilage and subchondral bone. These changes are not detectable by traditional arthroscopic means.     

A preliminary study of joint surface changes after an intraarticular fracture: a sheep model of a tibia fracture with weight bearing after internal fixation.

OBJECTIVE: To evaluate the changes in the articular cartilage and subchondral bone after an osteotomy designed to simulate an articular fracture. DESIGN: The contribution of the cartilage and subchondral bone was evaluated twelve weeks after creating a 1.0-millimeter step-off in the medial plateau of the tibia of twelve adult domestic sheep. All animals surviving were labeled with fluorescent markers for bone production, oxytetracycline (fifty milligrams per kilogram), and calcein (twelve milligrams per kilogram) nine and 11.5 weeks after surgery. The knees were loaded in compression using an Instron materials tester with pressure-sensitive film to record joint contact pressures above and below the medial meniscus. SETTING: The studies were performed in the research laboratories of the Orthopaedic Laboratory at Harborview Medical Center in Seattle, Washington and the Madigan Army Medical Center in Tacoma, Washington. ANIMALS: Twelve adult domestic sheep. INTERVENTION: An intraarticular osteotomy of the medial tibial plateau with 1.0 millimeter of displacement was performed. The osteotomy was stabilized with 3.5-millimeter lag screws. MAIN OUTCOME MEASURES: The contact pressures of the knee joint and articular histology were evaluated twelve weeks after surgery. Samples of the articular cartilage were analyzed by light microscopy and electron microscopy to evaluate the response of the articular cartilage and subchondral bone of the differential joint loading because of the irregularity in the articular surface caused by the osteotomy. RESULTS: The knees with an intraarticular step-off had two major contact areas with an intervening zone of reduced load corresponding to the edge of the depressed fragment. Coronal histologic sections through the articular surface showed the presence of thinning and fibrillation on the high side of the step-off and some compensatory hypertrophy of the cartilage. The subchondral bone was not responsible for restoring articular congruity because the rate of bone production was similar between the low side of the articular fracture (1.85 micrometers per day) and the high side of the fracture (1.67 micrometers per day). Scanning electron microscopy showed partial cartilage remodeling by deformation of the high side cartilage with bending of the vertical collagen fibrils, even in the unloaded state. CONCLUSIONS: In this model with a small fracture displacement (1.0 millimeter), which was less than the thickness of the articular cartilage (1.5 millimeters), the contour of the joint improved despite residual articular surface incongruency after the fracture healing.     

Studies of tibial subchondral bone density and its significance

We examined the relationships between the density of the subchondral bone of the proximal end of the tibia and the location and condition of the overlying articular cartilage and menisci. We took coronal sections of the tibial plateaus and of the overlying articular cartilage and menisci from human knee joints that were grossly free of osteoarthritis. The specimens were examined for the presence of cartilage fibrillation using the India-ink technique of Meachim. Bone density was determined using the Quantimet picture-point analyzer. Fibrillation of articular cartilage was observed only in the articular cartilage that was not covered by meniscus and lying mesial to it, which supports the concept that the meniscus confers a protective effect on the articular cartilage. The density of the bone underlying the meniscus was lower, and was inversely related to the thickness of the meniscus and directly related to the thickness of the articular cartilage. In four knees from which the menisci were absent, the bone density was increased at the periphery. We suggest that there is a trinitarian relationship between the meniscus, cartilage, and subchondral bone, in which structural changes in any one of the three causes secondary pathological adaptive changes in the other two.     

Role of subchondral bone in the initiation and progression of cartilage damage

Osteoarthrosis is a physiologic imbalance, a "joint failure" similar to "heart failure," in which mechanical factors play a role. The initiation and progression of cartilage damage are distinct phenomena. One of the mechanisms of initiation may be a steep stiffness gradient in the underlying subchondral bone. Progression of cartilage lesions probably requires stiffened subchondral bone. In such situations, transverse stresses at the base of the articular cartilage could cause deep horizontal splits in that tissue. The most likely cause of subchondral stiffening in an otherwise congruent joint is repeated failure of the musculoskeletal peak dynamic force attenuation mechanisms. The health and integrity of the overlying articular cartilage depends on the mechanical properties of its bony bed. In certain models of osteoarthrosis, alterations of the bony bed occur before the cartilage changes and suggest that this can occur in clinical conditions. Stiffening of the subchondral bone also can effect joint conformation, which involves deformation of articular cartilage and bone to create maximum contact areas under load.     

Absence of Proteoglycan 4 (Prg4) Leads to Increased Subchondral Bone Porosity Which Can Be Mitigated Through Intra‐Articular Injection of PRG4

Proteoglycan 4 (PRG4) is a mucin‐like glycoprotein important for joint health. Mice lacking Prg4 demonstrate degeneration of the cartilage and altered skeletal morphology. The purpose of this study was to examine if Prg4 deficiency leads to subchondral bone defects and if these defects could be mitigated through intra‐articular injection of recombinant human PRG4 (rhPRG4). Mice deficient in Prg4 expression demonstrated increased cartilage thickness and increased subchondral bone porosity compared with C57BL/6 controls. While the porosity of the subchondral bone of Prg4^?/? mice decreased over time with maturation, intra‐articular injection of rhPRG4 was able to forestall the increase in porosity. In contrast, neither hyaluronan (HA) nor methylprednisolone injections had beneficial effects on the subchondral bone porosity in the Prg4 knockout mice. Bone marrow progenitor cells from Prg4^?/? mice demonstrated reduced osteogenic differentiation capacity at 4 weeks of age, but not at 16 weeks of age. While most studies on PRG4/lubricin focus on the health of the cartilage, this study demonstrates that PRG4 plays a role in the maturation of the subchondral bone. Furthermore, increasing joint lubrication/viscosupplementation through injection of HA or controlling joint inflammation through injection of methylprednisolone may help maintain the cartilage surface, but had no positive effect on the subchondral bone in animals lacking Prg4. Therefore, alterations in the subchondral bone in models with absent or diminished Prg4 expression should not be overlooked when investigating changes within the articular cartilage regarding the pathogenesis of osteoarthritis/arthrosis. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2077–2088, 2019     

治疗关节软骨缺损手术方法的比较

目的对比研究骨膜移植术,软骨细胞移植术和骨软骨钻孔术对关节软骨损伤的修复。方法 纯种青紫蓝兔４４只,随机分为Ａ、Ｂ、Ｃ、Ｄ４组,在膝关节作全层软骨缺损模型,Ａ、Ｂ、Ｃ组分别选择行上述一种操作,Ｄ组不作处理。术后４、８、１２周取材作大体,光镜和电镜观察。结果 各组缺损均有不同程度修复,但修复优势组织性质有所差别。结论 自体游离骨膜移植术的钻孔术修复关节节软骨缺损效果明显优于未处理组,其中以钻孔术为简     

Scanning electron microscopic study of subchondral bone tissues in osteoarthritic femoral head]

In total hip replacement for 12 aged women with advanced osteoarthritis of the hip joint, three types of lesioned articular cartilage with various degrees of severity and ivory bone were obtained together with their subchondral bone tissues. These specimens were processed and studied under scanning electron microscope and were compared with sex and age-matched non-osteoarthritic femoral head articular cartilage specimens. In osteoarthritic femoral heads, with deepening of the articular lesion, the articular cartilage gradually became thinned out and eventually lost. The subchondral bone plate became markedly thickened in most of the specimens. The epiphyseal trabeculae were also thickened and turned rough so that the meshwork pattern gradually disappeared. The thickened trabeculae finally fused into a large piece of dense bone tissues without microfracture. These changes could be accounted for by the increased stress imposed on the subchondral bone tissues as a result of incompetence of the diseased articular cartilage. Consequently, the changes on the part of subchondral bone tissues of the osteoarthritic femoral heads were the sequent, rather than the cause, of the articular lesions.     

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.     

Effects of mechanical loading on the tissues of the rabbit knee

We studied changes in subchondral bone and articular cartilage in an animal model of osteoarthrosis. In this model we applied repetitive impulsive loads to rabbits' knees. Their legs were held in short leg splints so the rabbits were unable to dampen the peak applied load with ankle flexion. After sacrifice, at 1 day to 6 weeks, we studied proximal tibial load-bearing cartilage histologically, biochemically, and with radioactive sulfate uptake. We also studied the subchondral bone under that cartilage histologically, histomorphometrically, with bone scan (99mTc pyrophosphate), and by tetracycline labeling. An increase in 99mTc labeling of the subchondral bone was the first reliable change observed. This was followed by an increase in tetracycline labeling, bone formation, and a decrease in porosity, which has been associated with relative stiffening of bone. Horizontal splitting and deep fibrillation of the overlying articular cartilage followed the early bone changes. All of these changes preceded changes in content and characterization of cartilage proteoglycans or increased chondrocyte activity as manifested by incorporation of radioactive sulfate. In this model the early bone changes preceded changes in the articular cartilage. The deep splitting of articular cartilage occurred prior to metabolic alteration of that tissue.     

Articular cartilage degradation and de-differentiation of chondrocytes by the systemic administration of retinyl acetate-ectopic production of osteoblast stimulating factor-1 by chondrocytes in mice

OBJECTIVE: Vitamin A derivatives are widely used therapeutic agents for the treatment of dermatological and rheumatological disorders. Long-standing administration of these drugs, in turn, causes skeletal changes including ossification of ligaments, premature fusion of epiphyses and abnormalities of modeling. Recent in vitro experiments have further suggested that retinoid treatment of cultured chondrocytes may cause apoptotic cell death. The present study aims to address detailed cartilage changes associated with in vivo administration of vitamin A derivatives. METHODS: Retinyl acetate was administrated to experimental mice, C3H-Heston, for more than 12 months. Modified morphometry on the articular cartilage and fluorescent labeling of the subchondral bone were carried out to address the changes in the articular cartilage and subchondral bone. In order to address the detailed chondrocytes phenotypes, electron microscopy was carried out. Since findings of these studies suggested that biological properties of the cartilage matrix might be altered, the present study also immunolocalized functional matrix molecules, type I collagen and osteoblast-stimulating factor-1 (OSF-1). RESULTS: Histomorphometry demonstrated that retinoid administration lead to progressive atrophy of the articular cartilage with concomitant proliferation of subchondral bone. Furthermore, detailed light and electron microscopy suggested that the subchondral bone proliferates into the degenerating cartilage. The affected articular cartilage also resembled that of osteoarthritis in terms of ectopic type I collagen production. Furthermore, the affected articular cartilage produced a developmentally regulated matrix molecule, osteoblast-stimulating factor-1 (OSF-1) that is normally expressed in both the fetal cartilage and the epiphyseal growth plate cartilage but not in the articular cartilage. CONCLUSION: The present results indicate that the systemic retinoid administration may alter the biological properties of the articular cartilage.     

Osteochondral alterations in osteoarthritis

Osteoarthritis (OA) is a major cause of pain and disability in the aging population, but its pathogenesis remains incompletely understood. Alterations beneath the articular cartilage at the osteochondral junction are attracting interest as possible mediators of pain and structural progression in OA. Osteochondral changes occur early during the development of OA and may aggravate pathology elsewhere in the joint. Loss of osteochondral integrity removes the barrier between intra-articular and subchondral compartments, exposing subchondral bone and its nerves to abnormal chemical and biomechanical influence. Osteochondral plasticity results in a merging of tissue compartments across the junction. Loss of the clearly differentiated demarcation between bone and articular cartilage is associated with invasion of articular cartilage by blood vessels and sensory nerves, and advancing endochondral ossification. Increased subchondral bone turnover is intimately associated with these alterations at the osteochondral junction. Cells signal across the osteochondral junction, and this cross-talk may be both a consequence of, and contribute to these pathological changes. Bone turnover, angiogenesis and nerve growth are also features of other diseases such as osteoporosis and cancers, for which therapeutic interventions are already advanced in their development. Here we review pathological changes at the osteochondral junction and explore their potential therapeutic implications for OA. This article is part of a Special Issue entitled "Osteoarthritis".     

Effect of hip hemiarthroplasty on articular cartilage and bone in a canine model

The purpose of this study was to determine if acetabular articular cartilage damage occurs in the presence or absence of changes in subchondral plate thickness or porosity and trabecular bone architecture after hip hemiarthroplasty. Eight canines were sacrificed 6 months after receiving unilateral hemiarthroplasties in which a cobalt chrome alloy femoral head was used. The acetabular cartilage, subchondral plate, and trabecular bone were quantitatively evaluated. Although the articular cartilage in the treated hip showed gross and histologic degenerative changes, there were no differences in the treated and contralateral hips in any of the trabecular bone parameters or subchondral plate thickness. However, the subchondral plate porosity was increased 2.6-fold in the treated hip. Therefore, degradation of cartilage can occur in the absence of thickening of the subchondral plate or alterations in the supporting trabecular bone architecture. These observations provide a better understanding of the role that periarticular bone has in the degenerative process after hemiarthoplasty.     

膝关节原发性骨关节炎软骨和软骨下骨病理改变的定量研究

目的观察膝关节原发性骨关节炎(osteoarthritis,OA)胫骨平台软骨和软骨下骨病理改变特点,对比内、外侧平台软骨和软骨下骨结构参数,探讨钙化层和软骨下骨在OA发病机制中的作用。方法取2009年10月-2011年5月行人工全膝关节置换术治疗的30例30膝原发性OA患者自愿捐赠的新鲜胫骨平台标本进行实验。其中男11例,女19例;年龄55～78岁,平均65.1岁。病程10～25年,平均16.6年;患膝内翻畸形1～23°,平均9.3°。大体观察胫骨平台后在内、外侧中央负重区取材,常规制备脱钙石蜡切片,行HE和番红O/固绿染色,观察关节软骨退变特点,参照Mankin评分标准评分并分期;观察钙化层及软骨下骨病理改变。应用Image Pro Plus 6.0图像分析软件测量软骨和软骨下骨结构参数,包括软骨全层(total articular cartilage,TAC)厚度、钙化层(articular calcified cartilage,ACC)厚度、ACC/TAC比值、软骨下骨板(subchondral bone plate,SCP)厚度以及骨小梁体积分数(trabecular bone volume,BV/TV)。结果大体观察内侧平台软骨退变较外侧严重,内侧平台软骨Mankin评分为(12.4±1.1)分,显著高于外侧平台的(8.3±1.6)分(t=12.173,P=0.000)。根据Mankin评分结果在60个标本中,14个为OA早期,可见软骨浅表层裂隙、潮线复制和软骨下骨增厚;19个为OA中期,可见软骨深层裂隙、多发软骨下骨吸收陷窝和明显增厚的软骨下骨;27个为OA晚期,可见软骨全层缺失、软骨内化骨和"象牙化"软骨下骨。软骨和软骨下骨结构参数测定示:内侧平台TAC厚度显著低于外侧平台,ACC/TAC比值、BV/TV及SCP厚度显著高于外侧平台,差异均有统计学意义(P<0.05)。内、外侧平台ACC厚度比较,差异无统计学意义(P>0.05)。结论钙化层和软骨下骨可能在OA发生与进展中发挥了重要作用。     

Articular cartilage nutrition is mediated by subchondral bone: a long-term autograft study in baboons

OBJECTIVE: To determine the relative importance of subchondral nutrition in cartilage in autologous transplants and its relation to the development of osteoarthritis (OA). METHOD: The study was performed in non-human primates with two types of autografts placed orthotopically. One type of autograft was placed into vascularized, viable cancellous bone well, and another in an identical bone well, but coated with methylmethacrylate. The latter prevented direct contact between the autograft and the host bone. Observations were continued for 3 years. RESULTS: Abrogation of the contact between subchondral bone and articular cartilage-bone autograft had little effect on the cartilage during the first 5-12 months. By 3 years, autografts in the methylmethacrylate wells had non-vascularized and non-viable subchondral bone. The cartilage in these wells underwent degenerative changes compatible with OA. CONCLUSION: Interruption of contact between articular cartilage and vascularized subchondral bone resulted in degeneration of the cartilage. The onset and detection of these degenerative changes required long time periods (3 years). Had the experiments been terminated at 1 year or sooner the above described changes would not be apparent.     

Progressive cell‐mediated changes in articular cartilage and bone in mice are initiated by a single session of controlled cyclic compressive loading

We previously showed that repetitive cyclic loading of the mouse knee joint causes changes that recapitulate the features of osteoarthritis (OA) in humans. By applying a single loading session, we characterized the temporal progression of the structural and compositional changes in subchondral bone and articular cartilage. We applied loading during a single 5‐minute session to the left tibia of adult (26‐week‐old) C57Bl/6 male mice at a peak load of 9.0N for 1,200 cycles. Knee joints were collected at times 0, 1, and 2 weeks after loading. The changes in articular cartilage and subchondral bone were analyzed by histology, immunohistochemistry (caspase‐3 and cathepsin K), and microcomputed tomography. At time 0, no change was evident in chondrocyte viability or cartilage or subchondral bone integrity. However, cartilage pathology demonstrated by localized thinning and proteoglycan loss occurred at 1 and 2 weeks after the single session of loading. Transient cancellous bone loss was evident at 1 week, associated with increased osteoclast number. Bone loss was reversed to control levels at 2 weeks. We observed formation of fibrous and cartilaginous tissues at the joint margins at 1 and 2 weeks. Our findings demonstrate that a single session of noninvasive loading leads to the development of OA—like morphological and cellular alterations in articular cartilage and subchondral bone. The loss in subchondral trabecular bone mass and thickness returns to control levels at 2 weeks, whereas the cartilage thinning and proteoglycan loss persist. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1941–1949, 2016.