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Background: Osteochondral autologous transfer is one of the repair techniques for cartilage defects of knee with promising knee function recovery. There are no reports including histopathological images concerning human osteochondral tissue after osteochondral autologous transfer. This is the first report to present pathohistological findings of transplanted plugs and host tissues extracted from the human body 3 years after osteochondral autologous transfer. This study aimed to explore the cause factor of chronic pain using histological techniques., Case Presentation: A 67-year-old Japanese man presented with adjusted total knee arthroplasty 3 years after osteochondral autologous transfer. Although in pain, arthroscopic assessment was not severe. The specimens which was gained during total knee arthroplasty were investigated in gross and microscopically using immunohistochemical staining technic. Histological examination revealed that the gap between grafted plugs and host osteochondral tissues was filled with fibrous tissue that stained positive for type I collagen. A degenerative change and some neovascularity were observed in the regenerated tissue and host trabecular bone. Furthermore, cysts and bone marrow edema were observed., Conclusion: Our data suggests that the host osteochondral morbidity around grafted plugs might be related to chronical pain and revision surgery.

The purpose of this study was to examine the ultrastructural changes of surface cartilage collagen fibers, which differ by region and the length of the experimental period in an immobilization model of rat. Male Wistar rats were randomly divided into histological or macroscopic and ultrastructural assessment groups. The left knees of all the animals were surgically immobilized by external fixation for 1, 2, 4, 8 or 16 weeks (n = 5/time point). Sagittal histological sections of the medial mid-condylar region of the knee were obtained and assessed in four specific regions (contact and peripheral regions of the femur and tibia) and two zones (superficial and deep). To semi-quantify the staining intensity of the collagen fibers in the cartilage, picrosirius red staining was used. The cartilage surface changes of all the assessed regions were investigated by scanning electron microscopy (SEM). From histological and SEM observations, the fibrillation and irregular changes of the cartilage surface were more severe in the peripheral region than in the contact region. Interestingly, at 16 weeks post-immobilization, we observed non-fibrous structures at both the contact and peripheral regions. The collagen fiber staining intensity decreased in the contact region compared with the peripheral region. In conclusion, the alteration of surface collagen fiber ultrastructure and collagen staining intensity differed by the specific cartilage regions after immobilization. These results demonstrate that the progressive degeneration of cartilage is region specific, and depends on the length of the immobilization period., (© 2015 The Authors. Journal of Anatomy published by John Wiley & Sons Ltd on behalf of Anatomical Society.)

Background: Cartilage and subchondral bone have recently been considered an osteochondral unit. The treatment of osteochondral lesions is still challenging, but better subchondral bone repair may result in higher quality repaired cartilage., Hypotheses: Alendronate accelerates bone formation in osteochondral defects and affects the quality of the repaired cartilage., Study Design: Controlled laboratory study., Methods: Osteochondral defects were made on the left trochleas of 50 rabbits, which were assigned to 1 of 3 groups: control, ALN (weekly subcutaneous injection of 0.14 mg/mL alendronate), and ALN-S (alendronate injection in the first 8 weeks only). They were evaluated at 4, 8, 24, and 52 weeks. Bone repair was evaluated with microcomputed tomography and histologic evaluation. Cartilage repair was evaluated with ultrasound and histologic analyses., Results: At 4 weeks, the defects were filled, and cartilage-like repair tissue was observed in the ALN group, whereas the defects were incompletely filled in the control group. Alendronate treatment enhanced early bone formation and mineralization in the osteochondral defect for the first 8 weeks. The continuous injection of alendronate for 24 weeks resulted in delayed bone remodeling, but the rabbits in the ALN-S group showed good integrity of the subchondral bone plate, without delayed remodeling. At 52 weeks, the ALN-S group had a columnar arrangement of chondrocytes that had less fibrillation and looked superior to those in the ALN and control groups. Ultrasound analysis showed better quality of repaired cartilage of the ALN and ALN-S group than the control group., Conclusion: Alendronate accelerated bone formation without inhibiting its mineralization but thereafter inhibited bone remodeling in an osteochondral defect. The withdrawal of alendronate at 8 weeks avoided the delayed remodeling and showed better subchondral bone repair. At 52 weeks, better subchondral bone repair resulted in better cartilage quality., Clinical Relevance: Alendronate administered in the early period accelerates bone formation and improves the quality of the repaired cartilage.

Autogenous osteochondral grafts have become popular recently for use in small, isolated, contained articular cartilage defects. We treated a 35-year-old man who had cartilage defects, which were the same shape and probably the result of overuse, in the patellar grooves of both knee joints. The left side was 30 x 25 mm, and the right side was 17 x 17 mm in his right patellar groove, and 15 x 7 mm in his right medial femoral condyle. Therefore, we performed multiple osteochondral grafting of the bilateral lesions. Thirty-two months after his right knee operation (37 months after his left one), he had no pain or symptoms in his left knee and occasional mild pain and catching in his right knee. At second-look arthroscopy, the joint surface of the articular cartilage in the bilateral patellar groove was almost completely smooth. However, the whole of the weight-bearing area around the grafted plugs in the medial femoral condyle showed cartilage degeneration. Approximately 3 years after implantation of osteochondral grafts into similarly shaped cartilage lesions in the bilateral patellar grooves, the operative results were good. However, careful follow up is needed.

The purpose of this study was to clarify the histological effect of reducing the loading to knee on cartilage degeneration, osteophyte formation, and synovitis in early-stage osteoarthritis (OA) using a post-traumatic rat model. Ten male rats were randomly allocated into two experimental groups: OA induction by surgical destabilization of medial meniscus (DMM, OA group) and hindlimb suspension after OA induction by DMM (OAHS group). The articular cartilage, osteophyte formation, and synovial membrane in the medial tibiofemoral joint were analyzed histologically and histomorphometrically at 2 and 4 weeks after surgery. The histological scores and changes in articular cartilage and osteophyte formation were significantly milder and slower in the OAHS group than in the OA group. At 2 and 4 weeks, there were no significant differences in cartilage thickness and matrix staining intensity between both the groups, but chondrocytes density was significantly lower in the OA group. Synovitis was milder in OAHS group than in OA group at 2 weeks. Reducing knee joint loading inhibited histological OA changes in articular cartilage, osteophyte formation, and synovial inflammation. This result supports the latest clinical guidelines for OA treatment. Further studies using biochemical and mechanical analyses are necessary to elucidate the mechanism underlying delayed OA progression caused by joint-load reduction. [ABSTRACT FROM AUTHOR]

This study aimed to examine the effects of an episode of in vivo cyclic loading on rat knee articular cartilage (AC) under medium‐term observation, while also investigating relevant factors associated with the progression of post‐traumatic osteoarthritis (PTOA). Twelve‐week‐old Wistar rats underwent one episode comprising 60 cycles of 20 N or 50 N dynamic compression on the right knee joint. Spatiotemporal changes in the AC after loading were evaluated using histology and immunohistochemistry at 3 days and 1, 2, 4, and 8 weeks after loading (n = 6 for each condition). Chondrocyte vitality was assessed at 1, 3, 6, and 12 hours after loading (n = 2 for each condition). A localized AC lesion on the lateral femoral condyle was confirmed in all subjects. The surface and intermediate cartilage in the affected area degenerated after loading, but the calcified cartilage remained intact. Expression of type II collagen in the lesion cartilage was upregulated after loading, whereas the superficial lubricin layer was eroded in response to cyclic compression. However, the distribution of superficial lubricin gradually recovered to the normal level 4 weeks after loading‐induced injury. We confirmed that 60 repetitions of cyclic loading exceeding 20 N could result in cartilage damage in the rat knee. Endogenous repairs in well‐structured joints work well to rebuild protective layers on the lesion cartilage surface, which may be the latent factor delaying the progression of PTOA. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the histopathological changes in the patellofemoral joint using a rat model of osteoarthritis that was induced using monosodium iodoacetate, and to establish a novel model of patellofemoral osteoarthritis in a rat model using histopathological analysis. Sixty male rats were used. Osteoarthritis was induced through a single intra-articular injection of monosodium iodoacetate in both knee joints. Animals were equally divided into two experimental groups based on the monosodium iodoacetate dose: 0.2 mg and 1.0 mg. Histopathological changes in the articular cartilage of the patellofemoral joint and the infrapatellar fat pad were examined at 3 days, 1 week, 2 weeks, 4 weeks, 8 weeks, and 12 weeks after the monosodium iodoacetate injection. In the 1.0-mg group, the representative histopathological findings of osteoarthritis were observed in the articular cartilage of the patellofemoral joint over time. Additionally, the Osteoarthritis Research Society International scores of the patellofemoral joint increased over time. The synovitis scores of the infrapatellar fat pad in both groups were highest at 3 days, and then the values decreased over time. The fibrosis score of the infrapatellar fat pad in the 1.0-mg group increased with time, whereas the fibrosis score in the 0.2-mg group remained low. Representative histopathological findings of osteoarthritis were observed in the articular cartilage of the patellofemoral joint in a rat model of osteoarthritis induced using monosodium iodoacetate. With appropriate selection, this model may be regarded as an ideal patellofemoral osteoarthritis model. [ABSTRACT FROM AUTHOR]

An understanding of the articular cartilage degenerative process is necessary for the prevention and treatment of joint disease. The present study aimed to examine how long-term immobilization-induced cartilage degeneration is aggravated by remobilization. Sixty 8-week-old male Wistar rats were used in this study. The unilateral knee joint was immobilized using an external fixator for 8 weeks. The rats were killed at 0 and 3 days, and at 1, 2, 4 and 8 weeks after removing the fixator. After the rats were killed, the maximum knee extension angles were measured. Histological sections at the medial mid-condylar region (non-contact, transitional and contact regions of the femur and tibia) were prepared and scored. The cartilage thickness and number of chondrocytes were measured, and CD44 and Col2-3/4c expression levels were assessed immunohistochemically. The histological assessment revealed progressive aggravation of cartilage degeneration in the transitional region, with a decreased number of chondrocytes and CD44-positive chondrocytes as well as poor scoring over time, particularly in the tibia. Cyst formation was confirmed in the transitional region of the tibia at 8 weeks post-remobilization. The cartilage thickness in the transitional region was thicker than that in the contact region, particularly in the tibia. Col2-3/4c expression was observed in the non-contact and transitional regions, and the knee extension angle was recovered. In conclusion, immobilization-induced cartilage degeneration was aggravated by remobilization over time in the transitional region, followed by observations of a decreased number of chondrocytes and morphological disparity between different cartilage regions. [ABSTRACT FROM AUTHOR]

The repair of articular cartilage is challenging owing to the restriction in the ability of articular cartilage to repair itself. Therefore, cell supplementation therapy is possible cartilage repair method. However, few studies have verified the efficacy and safety of cell supplementation therapy. The current study assessed the effect of exercise on early the phase of cartilage repair following cell supplementation utilizing mesenchymal stromal cell (MSC) intra-articular injection. An osteochondral defect was created on the femoral grooves bilaterally of Wistar rats. Mesenchymal stromal cells that were obtained from male Wistar rats were cultured in monolayer. After 4 weeks, MSCs were injected into the right knee joint and the rats were randomized into an exercise or no-exercise intervention group. The femurs were divided as follows: C group (no exercise without MSC injection); E group (exercise without MSC injection); M group (no exercise with MSC injection); and ME group (exercise with MSC injection). At 2, 4, and 8 weeks after the injection, the femurs were sectioned and histologically graded using the Wakitani cartilage repair scoring system. At 2 weeks after the injection, the total histological scores of the M and ME groups improved significantly compared with those of the C group. Four weeks after the injection, the scores of both the M and ME groups improved significantly. Additionally, the scores in the ME group showed a significant improvement compared to those in the M group. The improvement in the scores of the E, M, and ME groups at 8 weeks were not significantly different. The findings indicate that exercise may enhance cartilage repair after an MSC intra-articular injection. This study highlights the importance of exercise following cell transplantation therapy. [ABSTRACT FROM AUTHOR]

ABSTRACT To date, there have been few studies on how temperature affects the phenotype and metabolism of human chondrocytes. Thus, the purpose of this study was to elucidate the effects of culture temperature on chondrocyte redifferentiation and extracellular matrix (ECM) formation using dedifferentiated mature human chondrocytes in vitro. Dedifferentiated chondrocytes were cultured in a pellet culture system for up to 21 days. The pellets were randomly divided into three groups with different culture temperature (32, 37, and 41°C). Chondrocyte redifferentiation and ECM formation were evaluated by wet weight, messenger ribonucleic acid (mRNA), histological, and biochemical analyses. The results showed that the wet weight and the mRNA expressions of collagen type II A1 and cartilage oligomeric matrix protein at 37°C were higher than the corresponding values at 32°C. The histological and biochemical analyses revealed that the syntheses of type II collagen and proteoglycan were promoted at 37°C compared to those at 32°C, whereas they were considerably inhibited at 41°C. In conclusion, the results obtained herein indicated that temperature affects chondrocyte redifferentiation and ECM formation, and modulation of temperature might thus represent an advantageous means to regulate the phenotype and biosynthetic activity of chondrocytes. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:633-639, 2015. [ABSTRACT FROM AUTHOR]

Recognizing subtle cartilage changes in the preclinical stage of osteoarthritis (OA) is essential for early diagnosis. To this end, the ability of the ultrasound signal intensity to detect macroscopically undetectable cartilage change was investigated. In this study, cartilage of rabbit OA model and human OA samples was examined by macroscopic evaluation, ultrasound signal intensity, histology with Mankin scores, and Fourier transform infrared imaging (FTIRI) analysis. Rabbit OA was induced by anterior cruciate ligament transection and evaluated at 1, 2, 4 and 12 weeks. Twenty human samples were harvested during total knee arthroplasty from OA patients who had macroscopically normal human cartilage (ICRS grade 0) on the lateral femoral condyle. In the animal study, there was no macroscopic OA change at 2 weeks, but histology detected degenerative changes at this time point. Ultrasound signal intensity also detected degeneration at 2 weeks. In human samples, all samples were obtained from macroscopically intact site, however nearly normal (0≤ Mankin score <2), early OA (2≤ Mankin score <6), and moderate OA (6≤ Mankin score <10) samples were actually intermixed. Ultrasound signal intensity was significantly different among these 3 stages and was well correlated with Mankin scores (R = −0.80) and FTIR parameters related to collagen and proteoglycan content in superficial zone. In conclusion, ultrasound can detect microscopic cartilage deterioration when such changes do not exist macroscopically, reflecting superficial histological and biochemical changes. [ABSTRACT FROM AUTHOR]

The aim was to use repeat delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) to estimate glycosaminoglycan (GAG) content in reparative cartilage after osteochondral autogenous transfer (OAT). The study group comprised 7 knees of 7 patients that were examined three times by dGEMRIC, at 3, 6, and 12 months using a 1.5 Tesla MRI system in both OAT operated and nonoperated condyles at 90 min after the injection. The gadolinium diethylene triamine pentaacetic acid (Gd-DTPA)2− containing contrast medium (0.2 mmols/kg) was injected intravenously. The mean T1 values of the plug cartilage at 3, 6, and 12 months after OAT was 230 ± 40, 213 ± 31, and 230 ± 23 ms (mean ± SD), respectively. There were differences between the plug and control cartilage at 3 ( p < 0.01) and 12 ( p < 0.05) months after OAT, but not at 6 months ( p = 0.089). No T1 changes were detected between the plug cartilage at the different time points after OAT. The fact that the GAG content of the OAT plugs were maintained for 12-month study period suggest that no major deterioration of load-bearing properties occurs in the cartilage after the OAT. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 30:221-225, 2012 [ABSTRACT FROM AUTHOR]

We previously developed a novel ultrasound assessment system featuring wavelet transform to evaluate the material properties of articular cartilage. We aimed in this study to demonstrate the feasibility of quantitative evaluation of meniscus using ultrasound and to elucidate the relationships between its acoustic, mechanical, and biochemical properties. Meniscal disc specimens from mature pigs were assessed by ultrasound and compression testing, and their correlation was analyzed. A positive correlation was found between the ultrasound signal intensity and apparent Young's modulus ( r = 0.61). Subsequently, the porcine meniscal discs were treated with various enzymes and then characterized by ultrasound, by compression tests, by biochemical analyses, and by histology and immunohistochemistry. The signal intensity was decreased not by hyaluronidase but by collagenase treatment. Hyaluronidase-treated menisci showed a discrepancy between acoustic and mechanical properties, suggesting that the ultrasound reflection could not detect a reduction in proteoglycan content. Also, ultrasound signal intensity could only reflect superficial layers of the material. Several limitations exist at present, and further studies and improvements of the device are required. However, given the noninvasive nature and the requirement of only small equipment, this ultrasound assessment system will be an instrumental diagnostic tool for meniscal function in both research and clinical fields. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 25:884-893, 2007 [ABSTRACT FROM AUTHOR]

Purpose: For successful autologous osteochondral transplantation, it is important that the cartilage in an implanted plug provide histologic replacement of damaged cartilage with cartilage that is structurally and mechanically normal. The purpose of this study was to investigate whether the press-fit technique reconstructs the normal hyaline cartilage and provides acoustic stiffness equal to that of normal intact cartilage. Methods: In 36 rabbits an osteochondral plug, 6 mm in diameter, was removed from the right patellar groove and grafted into a recipient hole, 5 mm in diameter, in the left patellar groove. Specimens at 2, 4, 8, 12, 24, and 52 weeks postoperatively were assessed by macroscopic and histologic observation and by use of an ultrasonic system. The ultrasonic acoustic stiffness, acoustic surface irregularity, and acoustic thickness of the implanted cartilage were examined and compared with normal intact cartilage. Results: The gross appearance of the implanted cartilage was glossy, maintained good surface smoothness, and survived well throughout the observation period. The cartilage recovered histologic features of hyaline cartilage. The acoustic stiffness decreased up to 12 weeks and then increased at 24 and 52 weeks after surgery. The acoustic stiffness at 8 or 12 weeks was significantly lower (acoustically softer) than that of control cartilage (P < .001). The acoustic stiffness at 52 weeks was equal to that of the control. The difference in acoustic surface irregularity was not significant. The acoustic thickness at 8 weeks was higher (acoustically thicker) than that of the control (P < .01). Conclusions: Although the reason acoustically soft cartilage in plugs becomes acoustically stiff and whether the histology of the implanted cartilage had recovered completely remain unclear, the acoustic stiffness recovered to normal control values by 52 weeks postoperatively. Clinical Relevance: Postoperative care for up to 12 weeks should be taken after autologous osteochondral transplantation. [ABSTRACT FROM AUTHOR]

This study was aimed at investigating the use of ultrasound parameters obtained non-invasively through soft tissue (ST) to evaluate degeneration in cartilage and subchondral bone (SB) in the human knee. We developed a 3-D ultrasound system and introduced the ratio parameters Rcb and RcbT to suppress the attenuation effect in the ST or in both the ST and cartilage. As reference measurements, the grade for cartilage by visual judgment (Gsum) and ultrasound parameters for the cartilage and the SB were directly evaluated under arthroscopy. Rcb correlated significantly with Gsum (rs = -0.63) and with the corresponding parameter obtained directly under arthroscopy (r = 0.55). RcbT also correlated significantly with Gsum (rs = -0.46) but was not superior to Rcb. Rcb is considered to be an efficient parameter that reflects the total degeneration in both the cartilage and SB, including the information on cartilage thickness. [ABSTRACT FROM AUTHOR]

The aim of this study was to identify ultrasound parameters reflecting subchondral porosity (Po), subchondral plate thickness (Tpl) and bone volume fraction at the trabecular bone region (BV/TVTb). Sixteen osteoarthritic human lateral femoral condyles were evaluated ex vivo using a 15-MHz pulsed-echo ultrasound 3-D scanning system. The cartilage-subchondral bone (C-B) surface region (layer 1) and inner subchondral bone region (layer 2) were analyzed; we newly introduced entropy (ENT) and correlation (COR) of ultrasound texture parameters of the parallel (x) or perpendicular (z) direction to the C-B interface for this analysis. Po, Tpl and BV/TVTb were evaluated as reference measurements using micro-computed tomography. ENTL1x (ENT of layer 1, x-direction) and ENTL1z were significantly correlated with Po (both r values = 0.58), CORL2x with Tpl (r = -0.73) and CORL2z with BV/TVTb (r = -0.66). These are efficient indicators of the characteristics of osteoarthritis-related subchondral bone; the other texture parameters were not significant. [ABSTRACT FROM AUTHOR]

We aimed to quantitatively investigate the relationship between amplitude-based pulse-echo ultrasound parameters and early degeneration of the knee articular cartilage. Twenty samples from six human femoral condyles judged as grade 0 or 1 according to International Cartilage Repair Society grading were assessed using a 15-MHz pulsed-ultrasound 3-D scanning system ex vivo. Surface roughness (Rq), average collagen content (A1) and collagen orientation (A12) in the superficial zone of the cartilage were measured via laser microscopy and Fourier transform infrared imaging spectroscopy. Multiple regression analysis with a linear mixed-effects model (LMM) revealed that a time-domain reflection coefficient at the cartilage surface (Rc) had a significant coefficient of determination with Rq and A12 (RLMMm2=0.79); however, Rc did not correlate with A1. Concerning the collagen characteristic in the superficial zone, Rc was found to be a sensitive indicator reflecting collagen disorganization, not collagen content, for the early degeneration samples. [ABSTRACT FROM AUTHOR]

We investigated the effect of low-intensity pulsed ultrasound (LIPUS) treatment combined with mesenchymal stromal cell (MSC) injection for cartilage repair and subchondral bone reconstitution for treatment of osteochondral defects. An osteochondral defect was created on both femur grooves of Wistar rats. Four weeks later, bone marrow MSCs were injected into the right knee joint. The rats were divided into two intervention groups: without or with LIPUS irradiation. Cartilage repair was evaluated histologically based on the Wakitani cartilage repair score. Subchondral bone reconstitution was evaluated as bone volume (BV)/tissue volume (TV) by micro-computed tomography analysis. MSC injection improved the cartilage repair score, and LIPUS irradiation improved BV/TV. Combination treatment promoted both cartilage repair and BV/TV improvement. Thus, MSC injection combined with LIPUS irradiation is more effective than either treatment alone in promoting concurrent cartilage repair and subchondral reconstitution. [ABSTRACT FROM AUTHOR]