Inhibition of fibrotic changes in infrapatellar fat pad alleviates persistent pain and articular cartilage degeneration in monoiodoacetic acid-induced rat arthritis model.

OBJECTIVE: We have reported that fibrotic changes in infrapatellar fat pad (IFP) after acute joint inflammation are closely associated with persistent pain in rats. In this study, to examine the effects of anti-fibrotic treatment on persistent pain, we used C-type natriuretic peptides (CNP) at the recovery phase after acute joint inflammation. DESIGN: Thirty-two male Wistar rats were used in this study. Monoiodoacetic acid (MIA) was injected intra-articularly to induce IFP fibrosis and persistent pain. CNP was injected after acute inflammatory phase in the same knee joint. Time-course pain-avoidance behavior tests and histological analyses were performed to examine the effects of CNP. RESULTS: Histological evaluations indicated that intra-articular injection of CNP inhibited fibrotic changes in IFP after acute inflammation. Incapacitance tests indicated that MIA injection into rat knee joint quickly decreased the percent weight on ipsilateral limb. In the vehicle group, the decrease was maintained up to day 28, suggesting that pain persistence occurred after acute inflammation (Day 0/Day 28, Est Dif -8.15, CI -10.78∼-5.53, Linear mixed-effect model). In contrast, the pain was alleviated in the CNP group after day 14 (Day0/Day 14, -0.51, -2.62-1.59). In addition, we observed significant improvement in the degree of articular cartilage degeneration at day 14 in the CNP group (OARSI score: vehicle 16.14 ± 4.37 vs CNP 6.87 ± 3.44, P < 0.01; Wilcoxon rank sum test). CONCLUSION: Fibrotic changes in IFP may play important roles in both persistent pain and articular cartilage degeneration.

Not single but periodic injections of synovial mesenchymal stem cells maintain viable cells in knees and inhibit osteoarthritis progression in rats.

OBJECTIVE: We investigated the effects of single or repetitive intra-articular injections of synovial mesenchymal stem cells (MSCs) on a rat osteoarthritis (OA) model, and elucidated the behaviors and underlying mechanisms of the stem cells after the injection. DESIGN: One week after the transection of the anterior cruciate ligament (ACL) of wild type Lewis rats, one million synovial MSCs were injected into the knee joint every week. Cartilage degeneration was evaluated with safranin-o staining after the first injection. To analyze cell kinetics or MSC properties, luciferase, LacZ, and GFP expressing synovial MSCs were used. To confirm the role of MSCs, species-specific microarray and PCR analyses were performed using human synovial MSCs. RESULTS: Histological analysis for femoral and tibial cartilage showed that a single injection was ineffective but weekly injections had significant chondroprotective effects for 12 weeks. Histological and flow-cytometric analyses of LacZ and GFP expressing synovial MSCs revealed that injected MSCs migrated mainly into the synovium and most of them retained their undifferentiated MSC properties though the migrated cells rapidly decreased. In vivo imaging analysis revealed that MSCs maintained in knees while weekly injection. Species-specific microarray and PCR analyses showed that the human mRNAs on day 1 for 21 genes increased over 50-fold, and increased the expressions of PRG-4, BMP-2, and BMP-6 genes encoding chondroprotective proteins, and TSG-6 encoding an anti-inflammatory one. CONCLUSION: Not single but periodic injections of synovial MSCs maintained viable cells without losing their MSC properties in knees and inhibited osteoarthritis (OA) progression by secretion of trophic factors.

Monoiodoacetic acid induces arthritis and synovitis in rats in a dose- and time-dependent manner: proposed model-specific scoring systems.

OBJECTIVE: In a rat monoiodoacetic acid (MIA)-induced arthritis model, the amount of MIA commonly used was too high, resulting in rapid bone destruction. We examined the effect of MIA concentrations on articular cartilage and infrapatellar fat pad (IFP). We also established an original system for "macroscopic cartilage and bone score" and "IFP inflammation score" specific to the rat MIA-induced arthritis model. DESIGN: Male Wistar rats received a single intra-articular injection of MIA in the knee. The amount of MIA was 0.1, 0.2, 0.5, and 1 mg respectively. Articular cartilage was evaluated at 2-12 weeks. IFP was also observed at 3-14 days. RESULTS: Macroscopically, low MIA doses induced punctate depressions on the cartilage surface, and cartilage erosion proceeded slowly over 12 weeks, while higher MIA doses already induced cartilage erosion at 2 weeks, followed by bone destruction. MIA macroscopic cartilage and bone score, OARSI histological score, and Mankin score increased in a dose- and time-dependent manner. The IFP inflammation score peaked at 5 days in low dose groups, then decreased, while in high dose groups, the IFP score continued to increase over 14 days due to IFP fibrosis. CONCLUSIONS: Punctate depressions, cartilage erosion, and bone destruction were observed in the MIA-induced arthritis model. The macroscopic cartilage and bone scoring enabled the quantification of cartilage degeneration and demonstrated that MIA-induced arthritis progressed in a dose- and time-dependent manner. IFP inflammation scores revealed that 0.2 mg MIA induced reversible synovitis, while 1 mg MIA induced fibrosis of the IFP body.

Synovial mesenchymal stem cells promote healing after meniscal repair in microminipigs.

OBJECTIVE: The induction of synovial tissue to the meniscal lesion is crucial for meniscal healing. Synovial Mesenchymal stem cells (MSCs) are an attractive cell source because of their high proliferative and chondrogenic potentials. We examined whether transplantation of synovial MSCs promoted healing after meniscal repair of extended longitudinal tear of avascular area in a microminipig model. DESIGN: Longitudinal tear lesion was made in medial menisci and sutured in both knees, and then a synovial MSC suspension was administered for 10 min only in unilateral knee. The sutured meniscus was evaluated morphologically and biomechanically at 2, 4, and 12 weeks. The behavior of transplanted MSCs was also examined. RESULTS: The meniscal healing at 12 weeks was significantly better in the MSC group than in the control group; macroscopically, histologically and by T1rho mapping analysis. Transmission electron microscopic analysis demonstrated that the meniscus lesion was occupied by dense collagen fibrils only in the MSC group. Biomechanical analysis revealed that the tensile strength to failure of the meniscus higher in the MSC group than in the control group in each microminipig. Synovial tissue covered better along the superficial layer from the outer zone into the lesion of the meniscus in the MSC group at 2 and 4 weeks in each microminipig. Synovial MSCs labeled with ferucarbotran were detected in the meniscus lesion and adjacent synovium by MRI at 2 weeks. CONCLUSION: Transplantation of synovial MSCs promoted healing after meniscal repair with induction of synovium into the longitudinal tear in the avascular zone of meniscus in pigs.

Repetitive allogeneic intraarticular injections of synovial mesenchymal stem cells promote meniscus regeneration in a porcine massive meniscus defect model.

OBJECTIVE: A new strategy is required in order to regenerate a meniscus for extensive defects. Synovial mesenchymal stem cells (MSCs) are an attractive cell source for meniscus regeneration due to their high proliferation and chondrogenic potential. We examined the effect of repetitive intraarticular injections of synovial MSCs on meniscus regeneration in a massive meniscal defect of pigs. We followed up the efficacy using MRI evaluation in addition to macroscopic and histological observations. DESIGN: Two weeks before the injection of synovial MSCs, the anterior half of the medial menisci was resected in both knees of pigs. Fifty million allogeneic synovial MSCs were injected into the right knee at 0, 2, and 4 weeks and followed up by sequential MRI. The regenerated meniscus, adjacent articular cartilage, and subchondral bone were evaluated by MRI at 2, 4, 8, 12 and 16 weeks. They were also evaluated macroscopically and histologically at 16 weeks (n = 7). RESULTS: The resected meniscus regenerated significantly better in the MSC group than in the control group based on histological and MRI analyses. Macroscopically, the meniscal defect already appeared to be filled with synovial tissue at 2 weeks. Articular cartilage and subchondral bone at the medial femoral condyle were also significantly more preserved in the MSC group based on MRI, macroscopic, and histological analyses. CONCLUSIONS: Intraarticular injections of allogeneic synovial MSCs appeared to promote meniscus regeneration and provide protection at the medial femoral articular cartilage in a porcine massive meniscal defect model.

Intra-articular injection of human mesenchymal stem cells (MSCs) promote rat meniscal regeneration by being activated to express Indian hedgehog that enhances expression of type II collagen.

OBJECTIVE: Meniscal regeneration was previously shown to be enhanced by injection of mesenchymal stem/stromal cells (MSCs) but the mode of action of the MSCs was not established. The aim of this study was to define how injection of MSCs enhances meniscal regeneration. DESIGN: A hemi-meniscectomy model in rats was used. Rat-MSCs (rMSCs) or human-MSCs (hMSCs) were injected into the right knee joint after the surgery, and PBS was injected into the left. The groups were compared macroscopically and histologically at 2, 4, and 8 weeks. The changes in transcription in both human and rat genes were assayed by species-specific microarrays and real-time RT-PCRs. RESULTS: Although the number of hMSCs decreased with time, hMSCs enhanced meniscal regeneration in a manner similar to rMSCs. hMSCs injection increased expression of rat type II collagen (rat-Col II), and inhibited osteoarthritis progression. The small fraction of hMSCs was activated to express high levels of a series of genes including Indian hedgehog (Ihh), parathyroid hormone-like hormone (PTHLH), and bone morphogenetic protein 2 (BMP2). The presence of hMSCs triggered the subsequent expression of rat-Col II. An antagonist of hedgehog signaling inhibited the expression of rat-Col II and an agonist increased expression of rat-Col II in the absence of hMSCs. CONCLUSIONS: Despite rapid reduction in cell numbers, intra-articular injected hMSCs were activated to express Ihh, PTHLH, and BMP2 and contributed to meniscal regeneration. The hedgehog signaling was essential in enhancing the expression of rat-Col II, but several other factors provided by the hMSCs probably contributed to the repair.

Magnesium enhances adherence and cartilage formation of synovial mesenchymal stem cells through integrins.

OBJECTIVE: We previously reported that more than 60% of synovial mesenchymal stem cells (MSCs) placed on osteochondral defects adhered to the defect within 10 min and promoted cartilage regeneration. The efficiency of adherence is considered to depend on the interaction between cells and extracellular matrix (ECM), in which integrins may play some important roles. Divalent cations such as calcium, magnesium, and manganese may affect functions of integrins, and the integrins may be involved in differentiation of MSCs. Among divalent cations, magnesium is used in clinical practice as a therapeutic agent and increases the affinity of integrin to ECM. In this study, we investigated whether magnesium enhanced adherence and chondrogenesis of synovial MSC through integrins. METHODS: We performed assays for adherence of human synovial MSCs to collagen-coated slides, in vitro chondrogenesis, ex vivo assays for adherence of human synovial MSCs to osteochondral defect, and in vivo assays for adherence and cartilage formation of synovial MSCs in a rabbit osteochondral defect model. RESULTS: Magnesium increased adhesion of human synovial MSCs to collagen, and this effect was inhibited by neutralizing antibodies for integrin α3 and ß1. Magnesium also promoted synthesis of cartilage matrix during in vitro chondrogenesis of synovial MSCs, which was diminished by neutralizing antibodies for integrin ß1 but not for integrin α3. Ex vivo analyses demonstrated that magnesium enhanced adherence of human synovial MSCs to osteochondral defects. In vivo studies in rabbits showed that magnesium promoted adherence at 1 day and cartilage formation of synovial MSCs at 2 weeks. CONCLUSION: Magnesium enhanced adherence of synovial MSCs through integrins, which promoted synthesis of cartilage matrix at an early phase.

Doppler ultrasonography-aided early diagnosis of venous thromboembolism after total knee arthroplasty.

OBJECTIVES: Postoperative deep venous thrombosis (DVT) is usually asymptomatic but can result in a fatal pulmonary embolism (PE). To assess the ability of transcranial Doppler (TCD) ultrasound apparatus to detect venous emboli in patients who had undergone total knee arthroplasty (TKA). METHODS: Forty-eight patients undergoing TKA were examined postoperatively by using compression ultrasonography, computed tomographic angiography, and TCD ultrasonography that detected high-intensity transient signals (HITS) in femoral veins. An original scoring system based on both the number of HITS and the locations of DVT was tested for its accuracy in predicting PE development. RESULTS: Twenty-three of the 48 patients had DVT postoperatively, and 8 had an asymptomatic PE. The sensitivity and specificity of the HITS assessment alone in identifying PE development were 75% and 92.5%, respectively. The scoring system, however, had a sensitivity of 100% and a specificity of 85% and the area under the receiver operating characteristic (ROC) curve (AUC) was 0.96. CONCLUSIONS: Application of a scoring system based on the detection of both DVT and HITS may be an effective and efficient method of screening for PE after knee arthroplasty.

Differences in kinematics of single leg squatting between anterior cruciate ligament-injured patients and healthy controls.

Seventy to eighty percent of all anterior cruciate ligament (ACL) injuries are due to non-contact injury mechanisms. It has been reported that the majority of injuries due to single leg landing come from valgus positioning of the lower leg. Preventing valgus positioning during single leg landing is expected to help reduce the number of ACL injuries. We found that many ACL-deficient patients cannot perform stable single leg squatting. Therefore, we performed 3D motion analysis of the single-legged half squat for ACL-injured patients to evaluate its significance as a risk factor for ACL injuries. We evaluated the relative angles between the body, thigh, and lower leg using an electromagnetic device during single leg half squatting performed by 63 ACL-injured patients (32 males, 31 females) the day before ACL reconstruction and by 26 healthy control subjects with no knee problems. The uninjured leg of ACL-injured male subjects demonstrated significantly less external knee rotation than that of the dominant leg of the male control. The uninjured leg of ACL-injured female subjects demonstrated significantly more external hip rotation and knee flexion and less hip flexion than that of the dominant leg of the female control. Comparing injured and uninjured legs, the injured leg of male subjects demonstrated significantly less external knee and hip rotation, less knee flexion, and more knee varus than that of the uninjured leg of male subjects. The injured leg of female subjects demonstrated more knee varus than that of the uninjured leg of female subjects. Regarding gender differences, female subjects demonstrated significantly more external hip rotation and knee valgus than male subjects did in both the injured and uninjured legs (P < 0.05). The current kinematic study exhibited biomechanical characteristics of female ACL-injured subjects compared with that of control groups. Kinematic correction during single leg half squat would reduce ACL reinjury in female ACL-injured subjects.

Atelocollagen-associated autologous chondrocyte implantation for the repair of chondral defects of the knee: a prospective multicenter clinical trial in Japan.

BACKGROUND: New tissue-engineering technology was developed to create a cartilage-like tissue in a three-dimensional culture using atelocollagen gel. The minimum 2-year followup outcome of transplanting autologous chondrocytes cultured in atelocollagen gel for the treatment of full-thickness defects of cartilage in knees was reported from the single institution. The present multicenter study was conducted to determine clinical and arthroscopic outcomes in patients who underwent atelocollagen-associated autologous chondrocyte implantation for the repair of chondral defects of the knees. METHODS: At six medical institutes in Japan, we prospectively evaluated the clinical and arthroscopic outcomes of transplanting autologous chondrocytes cultured in atelocollagen gel for the treatment of full-thickness defects of cartilage in 27 patients (27 knees) with cartilage lesions on a femoral condyle or on a patellar facet over 24 months. RESULTS: The Lysholm score significantly increased from 60.0 +/- 13.7 points to 89.8 +/- 9.5 points (P = 0.001). Concerning the ICRS grade for arthroscopic appearance, 6 knees (24%) were assessed as grade I (normal) and 17 knees (68%) as grade II (nearly normal). There were few adverse features, except for detachment of the graft in two cases. CONCLUSIONS: We concluded that transplanting chondrocytes in a newly formed matrix of atelocollagen gel can promote restoration of the articular cartilage of the knee.

Synovial fluid-derived mesenchymal stem cells increase after intra-articular ligament injury in humans.

OBJECTIVE: The existence of mesenchymal stem cells (MSCs) in SF was previously reported. However, the behaviour and properties of MSCs derived from SF have not been fully elucidated. METHODS: Human SFs were obtained from 19 knee joints with anterior cruciate ligament injury around the time of reconstruction surgery, and from three healthy volunteers. SF was plated, cultured and examined for colony-forming number, in vitro differentiation, surface epitopes and gene profiles. Also, rabbit synovium-MSCs were injected into the knee joint in a rabbit partial anterior cruciate ligament defect model, and the injected cells were traced. RESULTS: SF-MSCs from IA ligament injury patients were 100 times more in number than those from healthy volunteers. Total colony number was positively correlated with post-injury period. No significant differences were observed among the cells derived from SF around the time of the surgery in relation to surface epitopes and differentiation potentials. Cluster analysis of gene profiles demonstrated that SF-MSCs were more similar to synovium MSCs than bone marrow MSCs. In rabbit experiments, the MSCs injected into the knee in which IA ligament was partially defective were observed more on the defected area than on the intact area of the ligament at 24 h. CONCLUSION: We demonstrated that SF-MSCs, similar to synovium MSCs, increased in number after IA ligament injury and surgery without marked alteration of the properties.

ED-71, a novel vitamin D analog, promotes bone formation and angiogenesis and inhibits bone resorption after bone marrow ablation.

ED-71, a novel analog of 1alpha,25-(OH)2 D3, increases bone mass to a greater extent than alfacalcidol, an 1alpha,25-(OH)2 D3 prodrug. In this study, we used a murine bone marrow ablation model to compare the effect of ED-71 on bone formation and resorption in vivo with that of 1alpha,25-(OH)2 D3. We discovered that bone matrix remodeling occurring within the first week after bone marrow ablation was enhanced by a single injection of ED-71, but not by 1alpha,25-(OH)2 D3. This enhancement was associated with an increase in bone surface. Trabecular bone resorption occurring from 1 to 2 weeks after the procedure was suppressed by a single injection of ED-71, but not 1alpha,25-(OH)2 D3, with treated mice exhibiting a reduction in osteoclast numbers, despite increases in osteoblast surface. As seen with the single injection, daily administration of ED-71 also enhanced bone modeling. Bone marrow osteoblast differentiation was also augmented by ED-71 pretreatment. Furthermore, ED-71 treatment immediately after bone marrow ablation enhanced angiogenesis within the bone marrow cavity via enhancement of VEGF(120) expression. In this paper, we clearly demonstrate that ED-71 is an orally administered small molecular weight compound with an anabolic effect on bone metabolism.

Comparison of wear rate and osteolysis between second-generation annealed and first-generation remelted highly cross-linked polyethylene in total hip arthroplasty. A case control study at a minimum of five years.

BACKGROUND: There is no previous report that directly compared wear resistance of second-generation annealed highly cross-linked polyethylene with that of first-generation remelted highly cross-linked polyethylene. We therefore performed a retrospective study at a minimum of 5-year follow-up comparing second-generation annealed and first-generation remelted highly cross-linked polyethylene in order to: (1) assess wear rates and (2) compare the incidence of osteolysis between, (3) identify the frequency of complication related to the two types of highly cross-linked polyethylene. HYPOTHESIS: There is a difference in the linear wear rate and the incidence of osteolysis between the two types of highly cross-linked polyethylene in total hip arthroplasty. MATERIALS AND METHODS: In a single centre study, we reviewed 123 primary cementless total hip arthroplasties between 2010 and 2011 that were performed with 32mm alumina ceramic on second-generation annealed (X3) or first-generation remelted (Longevity) highly cross-linked polyethylene liner. There was no specific reason for the choice of the type of highly cross-linked polyethylene. There were no significant differences between the two groups in respect of gender, diagnosis, body mass index, pre- and post-operative functional and activity score, cup size, and cup orientation except the younger age in the X3 group. The mean wear rate and the incidence of osteolysis were evaluated at the latest follow-up. RESULTS: One hundred nine cases followed over 5 years post-operatively (88.6% in all consecutive cases) were evaluated. X3 and Longevity were used in 54 and 55 cases, respectively. The mean follow-up was 5.3 years in both groups. The mean linear wear rate of X3 and Longevity group was 0.045±0.023mm/year and 0.076±0.031mm/year, respectively (P<0.001). No osteolysis was found on plain X-rays in both groups and no specific complication was related to these highly cross-linked components. DISCUSSION: Excellent wear resistance of both types of highly cross-linked polyethylene liner was revealed in our study. The difference of wear rate between two materials should be monitored in a longer follow-up. LEVEL OF EVIDENCE: Level III retrospective case control study.

Comparison of wear rate and osteolysis between annealed and remelted highly cross-linked polyethylene in total hip arthroplasty. A case control study at 7 to 10 years follow-up.

BACKGROUND: Low polyethylene wear rate and low incidence of osteolysis after total hip arthroplasty using annealed and remelted highly cross-linked polyethylene have been reported. However, there is no previous report that directly compared both types of highly cross-linked polyethylene. We therefore performed a retrospective study on a series of highly cross-linked polyethylene, in order to: (1) compare wear rates and the incidence of osteolysis between annealed and remelted highly cross-linked polyethylene at 7-10 years; (2) identify the frequency of complication related to annealed and remelted highly cross-linked polyethylene. HYPOTHESIS: There is no difference in the linear wear rate and the incidence of osteolysis between the annealed and remelted highly cross-linked polyethylene in total hip arthroplasty. PATIENTS AND METHODS: Two hundred and sixteen cases of cementless total hip arthroplasties with annealed or remelted highly cross-linked polyethylene, which were performed between January 2003 and December 2006 in one institution, were followed for 7-10 years and received computed tomography scan, in addition to radiography at the latest follow-up. Annealed and remelted highly cross-linked polyethylene was used in 91 cases and 125 cases, respectively. A 26-mm cobalt-chromium head was used in all cases. Penetration rates from 1 year to the last evaluation were used to estimate the yearly linear wear rate. Existence of osteolysis was evaluated by plain radiography and computed tomography. RESULTS: There were no significant differences in patients' background between the two groups. The linear wear rate of annealed and remelted group was 0.031±0.022mm/year and 0.032±0.020mm/year, respectively (P=0.91). Two cases of small femoral osteolysis were found in the annealed group. Any complication related to highly cross-linked polyethylene was not found in both groups. DISCUSSION: There was no significant difference in the linear wear rate and the incidence of osteolysis between the annealed and remelted group at postoperative 7 to 10 years. Excellent results of both types of highly cross-linked polyethylene were revealed by this study. LEVEL OF EVIDENCE: Level III retrospective case control study.

Load affects remodeling of transplanted, autogenous bone-patellar tendon-bone segments in a rabbit model.

The question of whether or not load affects the remodeling of a transplanted autogenous free graft was addressed by removal of the patella-patellar tendon-tibial tubercle complex from the right knees of 15 New Zealand White rabbits. The tubercle was split, and the tendon was divided with each half trimmed to an equal width. The autograft complex was transplanted into a subcutaneous tunnel on the back of the rabbit. Controlled cyclic loads were applied via transcutaneous sutures to half of the graft, while the other half remained unloaded. The mechanical stiffness and strength and the cell density of loaded and unloaded halves of the autograft were measured in nine animals at 3 weeks and in six animals at 6 weeks. Five autografts from four additional rabbits served as unimplanted controls. An analysis of variance showed that the loaded portions of the autografts had a significantly higher failure strength (mean of 90%) and were significantly stiffer (mean of 62%) than the unloaded halves at 3 and 6 weeks. Failure strength was significantly greater (mean of 90%) at 3 weeks than at 6 weeks. The autografts were less stiff and had a lower failure strength than the unimplanted controls, with the greatest difference occurring in the unloaded segments at 6 weeks. Histology revealed that both loaded and unloaded segments demonstrated an increase in cellularity at 6 weeks compared with 3 weeks. This report introduces a model for the study of the effect of load on soft-tissue grafts and demonstrates that loading affects the remodeling process of a transferred autograft.

Sequential dynamics of monocyte chemotactic protein-1 expression in herniated nucleus pulposus resorption.

We previously demonstrated that the granulation tissues of herniated nucleus pulposus are composed of a marked infiltration of macrophages that strongly express monocyte chemotactic protein-1. Monocyte chemotactic protein-1 is a chemotactic cytokine that contributes to the activation and recruitment of macrophages. Relatively little is known about its role in the resorption process of herniated nucleus pulposus. To clarify the sequential dynamics of expression of monocyte chemotactic protein-1 in the granulation tissues of herniated nucleus pulposus, we introduced a rat autologous transplantation model of nuclear materials onto its lumbar dura mater and performed immunohistological analysis and competitive polymerase chain reaction assay using the grafted samples. Immunohistological analysis demonstrated that the majority of infiltrating mononuclear cells expressed monocyte chemotactic protein-1. Monocyte chemotactic protein-1 mRNA was expressed in the first 3 weeks after the procedure and was significantly and maximally upregulated at 1 week. To determine whether human recombinant monocyte chemotactic protein-1 facilitates the resorption process of herniated nucleus pulposus, we introduced another model of autologous transplantation, wherein the nuclear materials were grafted to the abdominal subcutaneous tissues and recombinant monocyte chemotactic protein-1 was subsequently applied to these materials. When monocyte chemotactic protein-1 was injected into the murine nucleus pulposus tissues, they reduced in size more rapidly than in the control group. These findings suggest that monocyte chemotactic protein-1 plays an important role in the recruitment of macrophages in the early phase of the resorption process of herniated nucleus pulposus and that its application may physiologically facilitate the resorption process of the nucleus pulposus.

Contrast-enhanced magnetic resonance imaging in conservative management of lumbar disc herniation.

STUDY DESIGN: This study was designed to investigate the morphologic changes in contrast-enhanced magnetic resonance imaging that occur during conservative treatment of patients with unilateral leg pain resulting from herniated nucleus pulposus without significant lumbar canal stenosis. OBJECTIVES: To compare the morphologic results with clinical outcomes to ascertain whether enhanced magnetic resonance imaging contributes to the management of lumbar disc herniation. SUMMARY OF BACKGROUND DATA: Contrast-enhanced magnetic resonance imaging has already been reported to be useful in the postoperative examination of the lumbar spine and in visualization of symptomatic nerve roots. However, there have been few reports about its usefulness in the conservative management of herniated nucleus pulposus or about the correlation between herniated nucleus pulposus regression and enhanced effect. The study population consisted of 48 patients with radiculopathy. All patients primarily reported unilateral leg pain, and 94% had positive tension signs. Additionally, 38% exhibited muscle weakness corresponding to the symptomatic nerve root. METHODS: All patients were studied twice or more using gadolinium-magnetic resonance imaging during conservative therapy, at a mean interval of 191 days. Changes in the size of the herniated nucleus pulposus on precontrast images fell into four categories, with changes in enhancement on postcontrast images classified into two categories: "enlargement" and "no change." RESULTS: In all cases of migrating type herniated nucleus pulposus, circular enhancement was seen on postcontrast images. In 17 of 22 cases, the enhanced area gradually thickened and intruded into the migrated disc materials as the size of the herniated nucleus pulposus decreased; the herniated nucleus pulposus disappeared in nine cases and showed a marked decrease in seven cases. These cases showed good clinical courses of sciatica. In the other five patients, in whom there were no changes in the enhanced area, there was less of a tendency for the herniated nucleus pulposus to decrease in size, and there were poorer clinical results. In six cases of extruding-type herniated nucleus pulposus, no enhanced effects were observed throughout the follow-up period. The other 20 cases showed enhancement that was relatively weaker than that of migrating disc herniation. Extension or expansion of the enhanced area was observed in the follow-up images of 15 cases, though only four showed obvious changes in the size of the herniated nucleus pulposus. These 15 cases had better clinical results than the other cases, in which enhanced effects did not change or were not observed. CONCLUSION: Contrast-enhanced magnetic resonance imaging is a useful prognostic parameter, and multiple use contributes to the proper management of lumbar disc herniation.

Dynamic motion study of the whole lumbar spine by videofluoroscopy.

STUDY DESIGN: Dynamic lumbar flexion-extension motion was assessed by videofluoroscopy. OBJECTIVES: To identify the motion patterns of the whole lumbar spine in normal subjects and in patients with low back pain or spondylolisthesis during actual movement. SUMMARY OF BACKGROUND DATA: Assessment of lumbar instability on terminal radiographs is controversial. Information regarding spinal kinematics during actual movement in vivo is scarce. METHODS: Fluoroscopic lumbar sagittal motion videos were recorded in volunteers (n = 13; mean age, 22.3) and in patients with chronic low back pain (n = 8; mean age, 43.5) and degenerative spondylolisthesis (n = 8; mean age, 63.1) while the subjects bent forward from a standing neutral position (eccentric motion) and then returned to the original position (concentric motion). The videos recorded approximately 8 seconds of motion and were converted to still images at 5 frames per second. Disc angles from the horizontal line were measured to estimate sagittal rotation of each segment. Disc degeneration was evaluated on T2-weighted midsagittal magnetic resonance image. RESULTS: In the volunteer group, six exhibited sequentially spreading motion, four exhibited simultaneous motion, and three showed an altered motion-spreading pattern in the eccentric phase. The first two patterns were considered normal. Six (67%) of the patients with chronic low back pain also showed normal patterns, but seven (88%) of the patients with degenerative spondylolisthesis showed disordered patterns. The order of motion in the concentric phase was also different among the three groups. Prolonged deflection of the slipped segment was observed more frequently in the patients with degenerative spondylolisthesis. Disc degeneration was not always associated with motion-spreading order and the motion patterns. CONCLUSION: Segmental instability influences the whole lumbar motion in patients with degenerative spondylolisthesis. The patients with chronic low back pain did not show a significant difference when compared with the volunteers.

Regression of cervical disc herniation observed on magnetic resonance images.

STUDY DESIGN: A retrospective study of cervical disc herniation using results of repeated magnetic resonance imaging examinations. OBJECTIVES: To clarify the cervical disc herniation morphological changes over time in order to establish a strategy for treatment. SUMMARY OF BACKGROUND DATA: In the authors' previous magnetic resonance imaging follow-up study of patients with lumbar disc herniation, spontaneous regression was observed in the sequestration-type lesions, and it was found that the tendency toward regression differed based on the anatomic position of extruded disc material. METHODS: Thirty-eight patients with cervical disc herniation who underwent repeated magnetic resonance imaging examinations were studied. The changes over time in herniated disc size were evaluated using this imaging technique. Evaluation showed the characteristics of those in whom spontaneous regression was found, such as extrusion pattern, and the clinical outcome was evaluated by symptoms. RESULTS: In 15 patients (40%), the volume of herniated material was decreased. The interval from onset of symptoms to the initial examination was significantly shorter in the regression group than in the group that showed no change in disc herniation. By extrusion pattern, cervical disc herniation, which was divided into migration type on sagittal view and lateral type on axial view, most frequently exhibited spontaneous regression. All of the patients with radicular pain and upper limb amyotrophy were treated successfully with conservative therapy. CONCLUSION: Although the possibility of the combination of hemorrhage and disc material could not be denied, active resorption of herniated material probably occurred during the acute phase. Extruded material exposed to the epidural space may be resorbed more quickly than that beneath the ligament. Vascular supply probably plays a role in the mechanism of resorption. The phase and position of extrusion were the significant factors affecting cervical disc herniation resorption. It was demonstrated that examination performed during the acute phase using magnetic resonance imaging is necessary for elucidation of the pathogenesis of cervical disc herniation, and that migrating, lateral-type herniations regress so frequently that conservative treatment should be chosen not only for patients with radicular pain, but also for those with upper limb amyotrophy.

Intercondylar notch width and its relation to the configuration and cross-sectional area of the anterior cruciate ligament. A cadaveric knee study.

If a narrow intercondylar notch contains a smaller anterior cruciate ligament, that may explain why people with narrow notches have a higher incidence of anterior cruciate ligament injuries. To investigate the significance of notch width measurement, we used 16 embalmed cadaveric knees. A positive mold of the entire anterior cruciate ligament, including its femoral and tibial insertions, was created with silicone rubber and plaster commonly used for dental molding. We had two hypotheses to test from this study. One was that the dimensions of the anterior cruciate ligament can be predicted by the notch width. The other was that the size of a person's anterior cruciate ligament can be predicted by a caliper measurement of the intercondylar notch. The width, sagittal length, and cross-sectional area of the midsubstance and the femoral and tibial insertions of the anterior cruciate ligament were measured. The notch width index, the ratio of notch width to width of the femoral condyle, showed a positive correlation only to the ratio of width to sagittal length of the tibial insertion. None of the parameters showed any differences between the knees with a notch width index less than or equal to 0.2 and those with a notch width index greater than 0.2. The knees with small notch width indexes did not have thinner anterior cruciate ligaments in them. These findings may not be applicable to knees obtained from other races, i.e., not Japanese.