Serum keratan sulfate is a promising marker of early articular cartilage breakdown.

OBJECTIVES: To find serum markers that may serve as indices for an early diagnosis of degeneration or damage of the articular cartilage. METHODS: Twenty-four healthy volunteers, 19 individuals with knee trauma (KT) and 31 with knee osteoarthritis (OA) were evaluated. KT patients were divided into a group (n = 5) with an injury <2 months old (recent KT) and a group (n = 14) with that >2 months old (old KT). Articular cartilage damage was assessed using either arthroscopy or direct observation. Serum concentrations of hyaluronic acid (HA), cartilage proteoglycan aggrecan turnover epitope (CS846) and cartilage oligomeric protein (COMP) were measured using enzyme-linked immunosorbent assay kits and those of keratan sulfate (KS) and chondroitin-6-sulfate (C6S) using high-performance liquid chromatography. RESULTS: Serum KS in the recent KT group (2095 +/- 594 ng/ml) was significantly higher than that in the old KT group (1373 +/- 418 ng/ml; P = 0.021), and serum COMP in the recent KT group (1572 +/- 182 ng/ml) showed a tendency that was higher than that in the old KT group (1350 +/- 250 ng/ml; P = 0.079). Serum KS in OA patients with Kellgren and Lawrence (KL) grades 0 and I (1456 +/- 334 ng/ml) showed a tendency that was higher than that in OA patients with KL grades II, III and IV (1248 +/- 220 ng/ml; P = 0.084). CONCLUSIONS: The serum concentration of KS correlated with the damage of the articular cartilage and it was significantly increased even at an early stage after the injury.

Treatment of a full-thickness articular cartilage defect in the femoral condyle of an athlete with autologous bone-marrow stromal cells.

OBJECTIVES: Human bone-marrow stromal cells are believed to be multipotent even in adults. This study assessed the effectiveness of autologous bone-marrow stromal cells, which were embedded within a collagen scaffold, to repair a full-thickness articular cartilage defect in the medial femoral condyle of an athlete. PATIENT AND METHODS: A 31-year-old male judo player suffering from pain in the right knee was reviewed. A 20 x 30-mm full-thickness cartilage defect (International Cartilage Repair Society classification (ICRS) grade IV) was revealed in the weight-bearing area of the medial femoral condyle. With the informed consent of the patient, the defect was treated with autologous bone-marrow stromal cells. Bone marrow was aspirated from the iliac crest of the patient 4 weeks before surgery. After removing the erythrocytes, the remaining cells were expanded in culture. Adherent cells were collected and embedded within a collagen gel, which was transferred to the articular cartilage defect in the medial femoral condyle. The implant was covered with an autologous periosteal flap. RESULTS: Seven months after surgery, arthroscopy revealed the defect to be covered with smooth tissues. Histologically, the defect was filled with a hyaline-like type of cartilage tissue which stained positively with Safranin-O. One year after surgery, the clinical symptoms had improved significantly. The patient had reattained his previous activity level and experienced neither pain nor other complications. CONCLUSIONS: Our findings indicate that the transplantation of autologous bone-marrow stromal cells can promote the repair of large focal articular cartilage defects in young, active patients.

Repair of articular cartilage defects in rabbits using CDMP1 gene-transfected autologous mesenchymal cells derived from bone marrow.

OBJECTIVE: Cartilage-derived morphogenetic protein 1 (CDMP1), which is a member of the transforming growth factor-beta superfamily, is an essential molecule for the aggregation of mesenchymal cells and acceleration of chondrocyte differentiation. In this study, we investigated whether CDMP1-transfected autologous bone marrow-derived mesenchymal cells (BMMCs) enhance in vivo cartilage repair in a rabbit model. METHODS: BMMCs, which had a fibroblastic morphology and pluripotency for differentiation, were isolated from bone marrow of the tibia of rabbits, grown in monolayer culture, and transfected with the CDMP1 gene or a control gene (GFP) by the lipofection method. The autologous cells were then implanted into full-thickness articular cartilage defects in the knee joints of each rabbit. RESULTS: During in vivo repair of full-thickness articular cartilage defects, cartilage regeneration was enhanced by the implantation of CDMP1-transfected autologous BMMCs. The defects were filled by hyaline cartilage and the deeper zone showed remodelling to subchondral bone over time. The repair and reconstitution of zones of hyaline articular cartilage was superior to simple BMMC implantation. The histological score of the CDMP1-transfected BMMC group was significantly better than those of the control BMMC group and the empty control group. CONCLUSION: Modulation of BMMCs by factors such as CDMP1 allows enhanced repair and remodelling compatible with hyaline articular cartilage.

Embryonic stem cells injected into the mouse knee joint form teratomas and subsequently destroy the joint.

OBJECTIVE: To determine whether the joint space is a suitable environment for embryonic stem (ES) cells to grow and form cartilage. METHOD: We transplanted ES cells into the knee joint and a subcutaneous space of mice with severe combined immunodeficiency. RESULTS: Teratomas formed in both areas. Those in the joints grew and destroyed the joints. The incidence of cartilage formation was the same in the knee joint and subcutaneous space, but the ratio of cartilage to teratoma was higher in the knee joint than in the subcutaneous space. The teratomas were proved to have been derived from the transplanted ES cells by detection of the neomycin-resistance gene that had been transfected into the ES cells. CONCLUSIONS: It is currently not possible to use ES cells to repair joint tissues. Further optimization of donor ES cells to differentiate as well as inhibit tumour growth may help to meet these challenges.

Substitution of Dmo1 with normal alleles results in decreased manifestation of diabetes in OLETF rats.

AIM: Dmo1 (Diabetes Mellitus OLETF type I) is a major quantitative trait locus for dyslipidaemia, obesity and diabetes phenotypes in the Otsuka Long Evans Tokushima Fatty (OLETF) rat strain. To evaluate possible metabolic and pathological improvements generated by correction of the Dmo1 genetic pathway, we produced congenic lines, in which both OLETF Dmo1 alleles are replaced by the F344-derived genome. METHODS: Congenic animals were produced by introgressing F344-derived Dmo1 alleles into the OLETF rat. Congenic animals of the fourth generation (BC4) were intercrossed to obtain F1 animals (BC4:F1). Animals of the next generation, BC4:F2, were used for this study. We used 23 BC4:F2 males harbouring homozygous replacement of the OLETF Dmo1 region with the F344-derived genome. Seven animals with OLETF-derived Dmo1 alleles were used as controls. RESULTS: Dmo1-F344/F344 congenic rats showed significant decreases in body weight, abdominal fat weight, serum triacylglycerols, total cholesterol, food consumption and blood glucose after glucose loading (13%, 39%, 45%, 27%, 18% and 27% respectively; p < 0.05) compared with Dmo1-OLETF/OLETF animals. Furthermore, histopathological analysis of the kidney showed that mesangial sclerosis, hyalin deposits and deposition of PAS-positive substance were significantly lower in Dmo1-F344/F344 animals (p < 0.05). CONCLUSION: Improvements in metabolic parameters and histopathological scores show that correction of the Dmo1 genetic pathway in the diabetic and mildly obese OLETF rat strain produces wide-ranging therapeutic effects. Thus, this pathway might represent a new drug target also applicable to humans.

Transplantation of cartilage-like tissue made by tissue engineering in the treatment of cartilage defects of the knee.

We investigated the clinical, arthroscopic and biomechanical outcome of transplanting autologous chondrocytes, cultured in atelocollagen gel, for the treatment of full-thickness defects of cartilage in 28 knees (26 patients) over a minimum period of 25 months. Transplantation eliminated locking of the knee and reduced pain and swelling in all patients. The mean Lysholm score improved significantly. Arthroscopic assessment indicated that 26 knees (93%) had a good or excellent outcome. There were few adverse features, except for marked hypertrophy of the graft in three knees, partial detachment of the periosteum in three and partial ossification of the graft in one. Biomechanical tests revealed that the transplants had acquired a hardness similar to that of the surrounding cartilage. We conclude that transplanting chondrocytes in a newly-formed matrix of atelocollagen gel can promote restoration of the articular cartilage of the knee.

A case report: reconstruction of a damaged knee following treatment of giant cell tumor of the proximal tibia with cryosurgery and cementation.

OBJECTIVE: Reconstruction of a knee damaged by cement packed to cure a giant-cell tumor is sometimes difficult. We reconstructed such a knee by removal of the cement, autologous bone transplantation and distraction osteogenesis using the Ilizarov apparatus. In this paper the results 29 months after the salvage surgery are given. PATIENT AND METHODS: We saw a 31-year-old woman's knee joint that showed osteoarthritic change after curettage, cryosurgery and cementation performed 4 years previously for a giant-cell tumor of the proximal tibia. We reconstructed the knee joint. This procedure included cement removal, alignment correction by tibial osteotomy, subchondral bone reconstruction by autologous bone transplantation, and filling the defect after removing the bone cement by elongating the diaphysis using the Ilizarov apparatus. RESULTS: Distraction was terminated 4 months later when 54 mm of elongation was performed. All devices were removed 12 months after the surgery. Seventeen months after the removal of the apparatus, the range of motion of the right knee was 0 degrees extension and 110 degrees flexion, and the patient was able to walk without pain. CONCLUSIONS: Although the treatment period is long and there may be some complications of Ilizarov lengthening and distraction osteogenesis, this procedure has numerous benefits. Bony defects can be soundly reconstructed and, at the same time, the alignment of the knee can be corrected. Also it is not necessary to reconstruct the ligaments because the insertions are intact. If osteoarthritis progresses, a surface type total knee replacement can be performed, not constrained type prosthesis, which would be used if the bony structure had not been reconstructed. This procedure may be one of the candidates for reconstructing such knee joints destroyed by bone cement.

Human autologous culture expanded bone marrow mesenchymal cell transplantation for repair of cartilage defects in osteoarthritic knees.

OBJECTIVE: There is no widely accepted method to repair articular cartilage defects. Bone marrow mesenchymal cells have the potential to differentiate into bone, cartilage, fat and muscle. Bone marrow mesenchymal cell transplantation is easy to use clinically because cells can be easily obtained and can be multiplied without losing their capacity of differentiation. The objective of this study was to apply these cell transplantations to repair human articular cartilage defects in osteoarthritic knee joints. DESIGN: Twenty-four knees of 24 patients with knee osteoarthritis (OA) who underwent a high tibial osteotomy comprised the study group. Adherent cells in bone marrow aspirates were culture expanded, embedded in collagen gel, transplanted into the articular cartilage defect in the medial femoral condyle and covered with autologous periosteum at the time of 12 high tibial osteotomies. The other 12 subjects served as cell-free controls. RESULTS: In the cell-transplanted group, as early as 6.3 weeks after transplantation the defects were covered with white to pink soft tissue, in which metachromasia was partially observed. Forty-two weeks after transplantation, the defects were covered with white soft tissue, in which metachromasia was observed in almost all areas of the sampled tissue and hyaline cartilage-like tissue was partially observed. Although the clinical improvement was not significantly different, the arthroscopic and histological grading score was better in the cell-transplanted group than in the cell-free control group. CONCLUSIONS: This procedure highlights the availability of autologous culture expanded bone marrow mesenchymal cell transplantation for the repair of articular cartilage defects in humans.

Greater tuberosity notch: an important indicator of articular-side partial rotator cuff tears in the shoulders of throwing athletes.

We examined the location of rotator cuff tears, associated labral injuries, and notches on the greater tuberosity of the humeral head in shoulders of throwing athletes. Arthroscopic findings (rotator cuff tear, labral condition, and greater tuberosity notch) as well as other factors (duration of playing baseball, range of motion, and joint laxity) of 61 baseball players were retrospectively studied. The presence of a greater tuberosity notch was also evaluated for by plain radiographs. Forty patients had articular-side partial rotator cuff tears, most of which occurred in the interval between the supraspinatus and infraspinatus tendons. The existence of a rotator cuff tear was not related to the range of motion, joint laxity, the detachment of the superior glenoid labrum, or posterosuperior labral injury. Greater tuberosity notches were recognized in 38 shoulders by arthroscopy and most were detected on plain radiographs. The presence of a notch was significantly related to the existence of a rotator cuff tear, while the size of the notch was significantly related to the depth and width of the tear. The greater tuberosity notch seems to be one of the most important diagnostic indicators for a rotator cuff tear in throwing athletes.

Effects of Dmo1 on obesity, dyslipidaemia and hyperglycaemia in the Otsuka Long Evans Tokushima Fatty strain.

Whole-genome scans have identified Dmo1 as a major quantitative trait locus (QTL) for obesity and dyslipidaemia in the Otsuka Long Evans Tokushima Fatty (OLETF) rat. We have produced congenic rats for the Dmo1 locus, using marker-assisted speed congenic protocols, enforced by selective removal of other QTL regions (QTL-marker-assisted counterselection), to efficiently transfer chromosomal segments from non-diabetic Fischer 344 (F344) rats into the OLETF background. In the third generation of congenic animals, we observed a substantial therapeutic effect of the Dmo1 locus on lipid metabolism, obesity control and plasma glucose homeostasis. We conclude that single-allele correction of an impaired genetic pathway can generate a substantial therapeutic effect, despite the complex polygenic nature of type II diabetic syndromes.

Single-allele correction of the Dmo1 locus in congenic animals substantially attenuates obesity, dyslipidaemia and diabetes phenotypes of the OLETF rat.

1. Whole-genome scans have identified Dmo1 as a major quantitative trait locus for dyslipidaemia and obesity in the Otsuka Long Evans Tokushima Fatty (OLETF) rat. 2. We have produced congenic rats for the Dmo1 locus through successive back-cross breeding with diabetic OLETF rats. Marker-assisted speed congenic protocols were applied to efficiently transfer chromosomal segments from non-diabetic Brown Norway (BN) rats into the OLETF background. 3. In the fourth generation of congenic animals, we observed a substantial therapeutic effect of the Dmo1 locus on lipid metabolism, obesity control and plasma glucose homeostasis. 4. We have concluded that Dmo1 primarily affects lipid homeostasis, obesity control and/or glucose homeostasis at fasting and is secondarily involved in glucose homeostasis after loading. 5. The results of the present study show that single-allele correction of a genetic defect of the Dmo1 locus can generate a substantial therapeutic effect, despite the complex polygenic nature of type II diabetic syndromes.

Japanese generalised osteoarthritis was associated with HLA class I--a study of HLA-A, B, Cw, DQ, DR in 72 patients.

To investigate the association between generalised osteoarthritis (GOA) and HLA-A, B, Cw, DQ and DR, we typed for HLA in 72 Japanese patients with GOA and compared with those of 1480 normal controls. The antigen frequency of HLA-Cw4 was significantly higher in the GOA group than in the control group. That of B62 was higher, but only uncorrected P values were significant. Those of HLA-Cw1 and Cw10 were significantly lower in the GOA group than in the control group. The antigen frequencies of HLA-DRB1*0101, *0401, *0405, *1001, and *1402, which were reported to be associated with rheumatoid arthritis, in the GOA group were not significantly different from those in the control group. The present study provides evidence of a significant association between Japanese GOA and HLA, which is different from that of Japanese RA. This may suggest that an immunological reaction that is different from RA plays a role in the pathogenesis of GOA.

Diagnostic imaging of unstable superior glenoid labral detachment: a comparison between MR arthrography and unenhanced MRI.

Abstract We compared efficacy of magnetic resonance arthrography (MRA) and magnetic resonance imaging (MRI) for the detection of superior glenoid labral detachment, and especially unstable superior labrum anterior-posterior (SLAP) type 2 lesions. MR imagings and MR arthrograms of 90 shoulders of 90 patients, including 30 shoulders of unstable SLAP 2 lesions, were interpreted by a novice and an expert observer. These results were correlated with arthroscopic findings. For the expert observer, MRI had a sensitivity of 53%, a specificity of 93%, and an accuracy of 80%, which were improved to 60%, 98%, and 85%, respectively, by MRA. These increases were statistically insignificant. For the novice observer, MRI had a sensitivity of 45%, a specificity of 80%, and an accuracy of 64%, which were significantly improved to 76%, 83%, and 80%, respectively, by MRA. In detecting unstable SLAP 2 lesions, MRA proved to be useful to a novice interpreter, but not significantly useful to an experienced interpreter, compared with unenhanced MRI. We advocate MRA as the examination of first choice for detecting unstable SLAP 2 lesions if they are strongly suspected clinically.

Huge tumor-like subacromial bursitis associated with rheumatoid arthritis.

Abstract We report a rare case of a huge subacromial bursitis in rheumatoid arthritis. A solid tumor was initially suspected because it was very large with no apparent local sign of inflammation, and because no fluid retention was observed. We performed radiograms, a plain computed tomogram, a (99)mTc-MDP bone scintigram, a (67)Ga-citrate scintigram, and a digital subtraction arteriogram, which all indicated no evidence of tumor. Finally, a bursogram proved the mass to be a huge enlarged subacromial bursa. Surgical exploration revealed that the bursa contained 450 g of a yellowish, jelly-like substance, which was considered to be a thick collection of fibrin. No recurrence was noted at a follow-up 16 years after surgery.

Quantitative trait loci for lipid metabolism in the study of OLETF x (OLETF x Fischer 344) backcross rats.

1. The Otsuka Long-Evans Tokushima Fatty (OLETF) rat is a model of type II diabetes with accompanying dyslipidaemia and obesity. 2. To define chromosomal intervals associated with obesity (abdominal fat weight and plasma leptin levels), dyslipidaemia (plasma triglyceride, cholesterol and free fatty acids) and hyperglycaemia (plasma glucose levels), we have performed genome-wide quantitative traits loci (QTL) analyses of 115 male OLETF x (OLETF x Fischer 344) backcross animals at 16 weeks of age. 3. The Diabetes Mellitus OLETF type I (Dmo1) locus on rat chromosome 1 showed statistically significant involvement in elevations of plasma levels of triglycerides (P = 4.87 x 10(-6) at D1Rat90) and total cholesterol (P = 1.16 x 10(-5) at D1Rat306). 4. No other loci produced significant linkage to these observed phenotypes. 5. These analyses have confirmed the importance of Dmo1 in lipid homeostasis at younger ages as well as during overt diabetes, which appears later. Thus, alterations at the Dmo1 locus are a major risk factor for pathogenesis in the strain, a finding that agrees with physiological studies that indicate a role for dyslipidaemia in the type II diabetic syndrome of OLETF rats.

Clinical experience with ceramics in total hip replacement.

As part of a search for better articulation in total hip prostheses, the decrease in the thickness of the socket in different total hip prostheses was measured in vivo. The wear rates of (1) RCH 1000 (molecular weight, 10(6)) socket gamma-irradiated with 100 Mrad articulating with a crude COP (stainless steel containing 20% cobalt and 0.01% phosphorous) metal femoral head; (2) RCH 1000 socket nonirradiated articulating with a crude COP femoral head; (3) RCH 1000 socket irradiated with 100 Mrad articulating with an alumina femoral head; (4) ultra high molecular weight polyethylene (molecular weight, 5-6 x 10(6)) socket articulating with an alumina femoral head; and (5) ultrahigh molecular weight polyethylene socket articulating with a stainless steel femoral head (T-28) were 0.06, 0.30, 0.06, 0.1 and 0.25 mm/year, respectively, in the authors' clinical cases. Alumina femoral heads were effective in decreasing wear of the polyethylene socket. However, the wear rates of gamma-irradiated sockets articulating with alumina and with metal femoral heads wear very low and were not different from each other. Regarding the relationship between wear rate and the thickness of the ultra high molecular weight polyethylene socket articulating with a 28 mm alumina femoral head, on radiographs, average wear rates of socket thicknesses of 7, 8, 9, 10 and 11 mm were 0.14, 0.15, 0.12, 0.06, and 0.08 mm/year, respectively. On measuring retrieved prostheses, average wear rates of 7, 8, 9 and 11 mm thickness sockets were 0.2, 0.19, 0.14, and 0.1 mm/year, respectively. The wear of sockets has been proven to be minimal in alumina femoral heads articulating with ultrahigh molecular weight polyethylene sockets thicker than 10 mm.

Modified Caspari technique for traumatic anterior shoulder instability: comparison of absorbable sutures versus absorbable plus nonabsorbable sutures.

The efficacy of the Caspari technique using a combination of absorbable and nonabsorbable sutures was compared with that of using only absorbable sutures. Forty-four patients (45 shoulders) underwent our modified Caspari technique for traumatic anterior shoulder instability and were followed-up for 2 to 3 years postoperatively. The average age at operation was 22 years. Among 27 patients treated using all absorbable PDS sutures, 7 patients had recurrent instability (success rate, 74%). Among 18 patients treated using both PDS and nonabsorbable polypropylene sutures, only one showed apprehension after a direct blow to the shoulder sustained by falling from a height (success rate, 94%). The mean stability score according to Rowe's criteria was significantly higher in the combination of absorbable and nonabsorbable group (P = .0412). External rotation increased more slowly in the combination of absorbable and nonabsorbable group than in the absorbable group. The mean limitation of external rotation was 8.4 degrees and 2.7 degrees, respectively (P = .0129). The modified Caspari technique using both absorbable and nonabsorbable sutures achieved excellent stability according to Rowe's criteria and external rotation showed more gradual improvement compared to repair with absorbable sutures alone.

Bankart procedure augmented by coracoid transfer for contact athletes with traumatic anterior shoulder instability.

We investigated the clinical efficacy of the Bankart procedure augmented by coracoid transfer for traumatic anterior shoulder instability in athletes playing contact sports. Eighty-three athletes (85 joints) with traumatic anterior shoulder instability who underwent the combined procedure were studied. The mean patient age at surgery was 21 years, and the mean follow-up period was 5.8 years (range, 2 to 12). According to the Rowe scoring system, the clinical results were graded as excellent for 58 shoulders, good for 21, fair for 5, and poor for 1, with an average score of 91 points. The overall success rate was 93%. A complete return to contact sports was achieved by 73 of the 83 patients (88%). The average loss of external rotation was 15 degrees with the arm at the side and 7 degrees with the arm in 90 degrees of abduction. The complications were nonunions in two cases, screw breakage in one case, and axillary nerve injury in one. This procedure can achieve a good clinical outcome for contact athletes with traumatic anterior shoulder instability.