Eccentric hip abductor weakness in patients with symptomatic external snapping hip.

Symptomatic external snapping hip can be a long-standing condition affecting physical function in younger people between 15-40 years. Gluteal weakness has been suggested to be associated with the condition. The aim of this study was to investigate whether eccentric hip abduction strength is decreased in patients with external snapping hip compared with healthy matched controls, and to examine isometric hip abduction, adduction, extension, flexion, internal rotation, and external rotation in patients with external snapping hip and matched controls. Thirteen patients with external snapping hip were compared with 13 healthy matched controls in a cross-sectional study design. The mean age of the patients was 25.5 ± 3.4 years and the mean age of the controls was 25.6 ± 2.6 years. Eccentric and isometric strength were assessed with a handheld dynamometer, using reliable test procedures. Eccentric hip abduction strength was 16% lower in patients with external snapping hip compared with healthy matched controls (1.50 ± 0.47 Nm/kg versus 1.82 ± 0.48 Nm/kg, P = 0.01). No other strength differences were measured between patients and controls (P > 0.05). Eccentric hip abductor weakness was present in patients with symptomatic external snapping hip compared with healthy matched controls.

Prospective 1-year follow-up study comparing joint prosthesis with tendon interposition arthroplasty in treatment of trapeziometacarpal osteoarthritis.

PURPOSE: Osteoarthritis of the thumb basal joint is a common and disabling condition. This clinical follow-up study compares the efficacy of total basal joint replacement surgery with that of tendon interposition arthroplasty. METHODS: Ninety-eight patients (mean age, 60 years +/- 1) with severe trapeziometacarpal joint osteoarthritis (Eaton-Littler stage 2.4 +/- 0.1) were included in this prospective follow-up study. Based on written and verbal information, the patients could choose either a cementless, unconstrained, hydroxyapatite-coated trapeziometacarpal joint prosthesis or abductor pollicis longus tendon interposition arthroplasty. Clinical outcome parameters were determined preoperatively and at 3, 6, and 12 months postoperatively. Furthermore, osteo-integration and osteo-fixation of the implants were radiologically analyzed after 12 months. RESULTS: Joint replacement surgery resulted in faster and better pain relief, stronger grip functions, improved range of motion, and faster convalescence than did tendon interposition arthroplasty. After 12 months, patients with joint prostheses had regained the same strength and range of motion as in the asymptomatic contralateral thumb. After 12 months, osteolysis had developed in the vicinity of 2 cups, but there were no signs of implant loosening. The prosthesis surgery was not associated with more complications than occurred with tendon interposition arthroplasty. CONCLUSIONS: This study demonstrates that patients with joint prostheses achieve faster convalescence with better patient comfort and improved strength and range of motion without any increased risk of complications than do patients treated with tendon interposition arthroplasty at 1-year follow up. However, a randomized clinical trial with long-term follow-up is required.

Adeno-associated vector mediated gene transfer of transforming growth factor-beta1 to normal and osteoarthritic human chondrocytes stimulates cartilage anabolism.

The objective of the present study was to investigate whether cartilage anabolism in human primary osteoarthritic chondrocytes could be improved by adeno-associated virus (AAV) vector-mediated gene transduction of transforming growth factor TGF-beta1 (TGF-beta1). A bi-cistronic AAV-TGF-beta1-IRES-eGFP (AAV-TGF-beta1) vector was generated and used for transduction of a normal human articular chondrocyte cell line (tsT/AC62) and primary human osteoarthritic articular chondrocytes harvested from 8 patients receiving total knee joint arthroplasty. Transduction efficiency was detected by fluorescent microscopy for gene expression of enhanced green fluorescent protein (eGFP). TGF-beta1 synthesis was determined by ELISA. To assess the influence of TGF-beta1 gene therapy on chondrocyte cartilage metabolism, mRNA expressions of type II collagen, aggrecan, and matrix metalloproteinase 3 (MMP-3) were determined by quantitative real-time PCR. AAV-TGF-beta1 transduction resulted in increased synthesis of TGF-beta1 in both osteoarthritic chondrocytes and the normal articular chondrocyte cell line. The expression levels of the transduced genes were correlated to "multiplicity of infection" (MOI) and post-infectious time. In both osteoarthritic chondrocytes and the normal articular chondrocyte cell line, AAV-TGF-beta1 treatment increased mRNA expression of both type II collagen and aggrecan, but decreased MMP-3 mRNA expression. Osteoarthritic chondrocytes and the normal articular chondrocyte cell line could be transduced with equal efficiencies. In conclusion, it was demonstrated that AAV-TGF-beta1 gene transfer stimulates cartilage anabolism and decreases expression of enzymes responsible for cartilage degradation in human osteoarthritic chondrocytes. The results indicate that the AAV vector is an efficient mediator of growth factors to human articular chondrocytes, and that it might be useful in future chondrocyte gene therapy.

In vivo gene delivery to articular chondrocytes mediated by an adeno-associated virus vector.

PURPOSES: (1) To investigate the efficiency of direct in vivo adeno-associated virus (AAV) vector-mediated gene transduction to chondrocytes in relation to normal and injured articular cartilage. (2) To evaluate the effects of ultra-violet light-activated gene transduction (LAGT) in chondrocytes in vivo. (3) To determine dissemination of active rAAV vector after intra-articular administration. METHODS: Rabbit knees with either normal or injured cartilage received an intra-articular injection with 1.5x10(12) infectious rAAV-eGFP particles. The right knees received rAAV-eGFP alone, whereas the left knees were given LAGT-treatment. The transduction efficiencies were determined at 1 and 3 weeks after infection by fluorescence-activated cell scanning. The occurrence of active shedding was monitored in serum and various tissues. RESULTS: After 1 week, 7% of the chondrocytes in normal cartilage were transduced by direct rAAV transduction technique. Chondrocytes in cartilage defects demonstrated higher transduction rates compared to chondrocytes in normal cartilage. LAGT increased the cellular eGFP expression in the internal zones to 12%, but did not have any effect in the external zones in defects. Finally, infectious particles were not detected in either serum or tissue samples. CONCLUSIONS: Direct rAAV-mediated gene transfer in vivo to articular chondrocytes is possible. LAGT improves rAAV transduction of chondrocytes in vivo but appears to have a very limited range of effect induction. Expression of eGFP was not determined in other tissues than synovium and cartilage in the treated joints.

Effect of oxygen concentration, culture format and donor variability on in vitro chondrogenesis of human adipose tissue-derived stem cells.

BACKGROUND: The chondrogenic differentiation potential of the easily accessible adipose tissue-derived stem cells (ASCs) is of particular interest within the field of tissue engineering for treating cartilage defects. However, no consensus has been reached as to which oxygen tension is more beneficial for the differentiation process. MATERIALS & METHODS: In this investigation, the impact of available oxygen was investigated to identify optimal conditions for human ASC chondrogenesis in vitro. Four physiologically relevant oxygen concentrations of 15, 10, 5 and 1% were compared with ambient air condition, and the ASCs originating from six unrelated donors were subjected to chondrogenic induction in high-density pellet cultures. RESULTS: The qualitative and quantitative assessment of accumulated extracellular matrix and the gene-expression analysis revealed marked interindividual differences, nevertheless the chondrogenic process was optimally supported in high-density pellet setup at ambient or 15% oxygen concentrations, irrespective of the origin of cells. The histochemical analysis based on alcian blue staining demonstrated that the differentiation took place in a gradient-like fashion, displaying highest levels in restricted regions, most often adjacent to the periphery. The two lowest hypoxic conditions, at 5 and 1% oxygen, seemed to have an inhibitory effect. CONCLUSION: The micropellet cultures at ambient or 15% oxygen concentration provided the most suitable environment for inducing chondrogenesis in ASCs. Furthermore, in light of the fact that the induction appeared in a zone-dependent manner, this format lends itself as a suitable model for further analysis of the relationship between chondrogenic differentiation and the gradient of nutrients.

Osteoprotegerin treatment impairs remodeling and apparent material properties of callus tissue without influencing structural fracture strength.

The influence of osteoprotegerin (OPG) treatment on callus formation, callus tissue structural strength, apparent material properties, and histology of tibia fractures in rats was investigated after 3 weeks and 8 weeks of healing. OPG was given intravenously (10 mg/kg twice weekly) during the entire observation period, and control animals with fractures received vehicle only. When compared with control fractures after 3 weeks of healing, OPG treatment reduced the number of osteoclasts in the callus tissue (93%, P < 0.001) and hampered resorption of genuine cortical bone in the fracture line; OPG treatment did not influence callus dimensions, callus bone mineral content (BMC), fracture structural strength, or callus tissue apparent material properties. When compared with control fractures after 8 weeks of healing; OPG treatment reduced the number of osteoclasts in callus tissue (92%, P < 0.001), augmented callus dimensions (anteriorposterior diameter: 12%, P = 0.034, mediolateral diameter: 13%, P = 0.013), and increased callus BMC (50%, P = 0.007); OPG treatment hampered deposition of new woven bone at the fracture line of the genuine cortical bone (new woven bone present in all vehicle animals, but only in 13% of the OPG-treated animals (P < 0.001)); OPG treatment did not influence structural strength of the fractures, but decreased apparent material properties of the callus tissue (ultimate stress: 51%, P < 0.001; elastic modulus: 42%, P = 0.033). The experiment demonstrates that OPG treatment does not influence the early callus expansion and fracture strength. However, during the subsequent period of remodelling, OPG treatment impairs the normal remodeling and consolidation processes.