Metabolism of Subchondral Bone Tissue in Posttraumatic Osteoarthrosis in Rats.

In rats with modeled posttraumatic knee osteoarthrosis, negative changes in subchondral bone metabolism were revealed: a tendency to an increase in osteocalcin concentration, a decrease in sclerostin and osteoprotegerin levels, and a significant increase in FGF-23 concentration accompanied by a slight elevation of inorganic phosphorous and significant increase in total calcium levels in comparison with the corresponding parameters in intact controls. These findings demonstrate crucial importance of structural integrity of the subchondral bone, because its protection improves the results of reconstructive therapy for local cartilage defects.

Vague Posterior Knee Discomfort in a Soccer Player: A Clinical Vignette.

A 24-yr-old male soccer player presented with a 7-yr history of left posterior knee "looseness." Evaluation 7 yrs ago, at the time of initial injury, revealed atraumatic anterior and posterior cruciate ligament sprains. On representation, the patient described the pain as a constant, dull ache, 3/10, but his biggest complaint was this feeling of "instability" and looseness where his knee would "buckle" 3-4 times a week. Physical examination was positive for grade 1 posterior drawer and grade 1 posterior sag signs. Reverse KT-1000 testing showed a 3-mm side-to-side difference. Sonographic evaluation confirmed magnetic resonance imaging findings of posterior cruciate ligament laxity and buckling and a small cystic lesion abutting the posteromedial margin of the distal 1/3 of the posterior cruciate ligament. After a trial of physical therapy, the patient elected to undergo experimental injection of dextrose hyperosmolar solution. This resulted in resolution of the cyst and reverse KT-1000 measurements improved to a side-to-side difference of 1 mm. The patient's subjective feeling of looseness and instability resolved by 7 wks.

Platelet rich concentrate enhances mesenchymal stem cells capacity to repair focal cartilage injury in rabbits.

BACKGROUND: It has been previously suggested that the use of regenerative promoters, which include bone marrow-derived mesenchymal stem cells (MSCs) or natural growth factors supplement such as platelet-rich concentrate (PRC) could promote cartilage regeneration. However, the notion that the concurrent use of both promoters may provide a synergistic effect that improves the repair outcome of focal cartilage injury has not been previously demonstrated. This study was thus conducted to determine whether the concomitant use of PRC could further enhance the reparative potential of MSCs encapsulated in alginate transplanted into focal cartilage injury in rabbits. METHODS: Artifically created full thickness cartilage defects were made on the weight-bearing region of medial femoral condyles in bilateral knees of New Zealand White rabbits (N = 30). After one month, the right knee was treated with either i) PRC (n = 10), ii) MSCs (n = 10), or, iii) a combination of PRC and MSCs (PRC + MSC) (n = 10), all encapsulated in alginate. The left knee remained untreated (control). Rabbits were sacrificed at 3 and 6 months after treatment. Cartilage tissue regeneration was accessed using ICRS morphologic scoring, histologic grading by O'Driscoll scoring, immunohistochemical staining and quantitative analysis of glycosaminoglycans (GAG) per total protein content. RESULTS: At 3 months, transplantation using PRC alone was equally effective as MSCs in inducing the repair of cartilage defects. However, PRC + MSC resulted in significantly higher ICRS and O'Driscoll scores (p < 0.05) as compared to other groups. The regenerated tissues from the PRC + MSC group also had stronger staining for Safranin-O and collagen type II. By 6 months, in addition to superior ICRS and O'Driscoll scores as well as stronger staining, glycosaminoglycan per total protein content was also significantly higher (p < 0.05) in the PRC + MSC group (3.4 ±â€¯0.3 µg/mg) as compared to the MSC (2.6 ±â€¯0.2 µg/mg) or PRC (2.1 ±â€¯0.2 µg/mg) groups. CONCLUSION: PRC enhances the reparative effects of MSC in treating focal articular cartilage injuries.

Isolated lateral collateral ligament complex injury in rock climbing and Brazilian Jiu-jitsu.

We report two occurrences of high-grade tears of the lateral collateral ligament complex (LCLC), consisting of the anterolateral ligament (ALL) and fibular collateral ligament (FCL). One injury occurred in a rock climber and the other in a martial artist. Increasing awareness of isolated injuries of the LCLC will allow for appropriate diagnosis and management. We review and discuss the anatomy of the LCLC, the unique mechanism of isolated injury, as well as physical and imaging examination findings.

Effect of intra-articular local anesthesia on articular cartilage in the knee.

PURPOSE: To evaluate the hypothetical toxic effect of local anesthetics on the articular cartilage using patient data from autologous chondrocyte cultivation with different anesthesia types used for arthroscopic cartilage biopsy specimen procurement. METHODS: A retrospective analysis of patient data from the national autologous chondrocyte implantation registry and the corresponding hospital records was approved by the National Medical Ethics Committee. Articular cartilage biopsy specimens from the knees of 49 consecutive patients assigned for autologous chondrocyte implantation (aged 14 to 44 years) were procured from the non-weight-bearing articular surface during arthroscopy under general anesthesia (12 patients), spinal anesthesia (18 patients), or local anesthesia (intra-articular injection of 15 to 20 mL of 2% lidocaine hydrochloride) (19 patients). All the biopsy specimens were further manipulated following the same chondrocyte cultivation protocol. General patient data and surgery-related parameters, together with chondrocyte viability, population doublings, and chondrocyte morphology in biopsy specimens and primary cell cultures, were analyzed and compared across different types of anesthesia. RESULTS: Patients in the general, spinal, and local anesthesia groups showed no statistical differences in age (27 years, 29 years, and 32 years, respectively), duration of surgery (36 minutes, 37 minutes, and 39 minutes, respectively), weight of biopsy specimens (110 mg, 178 mg, and 130 mg, respectively), cell viability in cartilage biopsy specimens (67%, 69%, and 78%, respectively) or primary cultures (95%, 95%, and 95%, respectively), and population doublings (5.2, 5.2, and 5.2, respectively). Similar chondrocyte morphology in primary cell cultures was observed among the 3 groups. CONCLUSIONS: This retrospective study showed that a single intra-articular injection of lidocaine hydrochloride used for knee arthroscopy did not influence the viability, morphology, and cultivation potential of chondrocytes in articular cartilage biopsy specimens assigned for autologous chondrocyte implantation. LEVEL OF EVIDENCE: Level IV, retrospective comparative study.

Accelerated and increased joint damage in young mice with global inactivation of mitogen-inducible gene 6 after ligament and meniscus injury.

INTRODUCTION: Ligament and meniscal damage can cause joint disease. Arthritic joints contain increased amounts of epidermal growth factor receptor (EGFR) protein, and polymorphisms in EGFR are associated with arthritis risk. The role of endogenous EGFR regulation during joint disease due to ligament and meniscal trauma is unknown. Mitogen-inducible gene 6 (MIG-6) can reduce EGFR phosphorylation and downstream signaling. We examined the effect of EGFR modulation by MIG-6 on joint disease development after ligament and meniscus injury. METHODS: Knee ligament transection and meniscus removal were performed surgically on mice homozygous for a global inactivating mutation in MIG-6 (Mig-6⁻/⁻) and in wild-type (WT) animals. RESULTS: Two weeks after surgery, Mig-6⁻/⁻mice had bone erosion as well as greater fibrous tissue area and serum RANKL concentration than WT mice. Four weeks after surgery, Mig-6⁻/⁻mice had less cartilage and increased cell proliferation relative to contralateral control and WT knees. Increased apoptotic cells and growth outside the articulating region occurred in Mig-6⁻/⁻mice. Tibia trabecular bone mineral density (BMD) and the number of trabeculae were lower in surgically treated knees relative to the respective control knees for both groups. BMD, as well as trabecular thickness and number, were lower in surgically treated knees from Mig-6⁻/⁻mice relative to WT surgically treated knees. Phosphorylated EGFR staining in surgically treated knees decreased for WT mice and increased for Mig-6⁻/⁻mice. Fewer inflammatory cells were present in the knees of WT mice. CONCLUSION: Mig-6⁻/⁻mice have rapid and increased joint damage after ligament and meniscal trauma. Mig-6 modification could lessen degenerative disease development after this type of injury.

Low-level laser therapy in meniscal pathology: a double-blinded placebo-controlled trial.

We performed a randomized, double-blinded, placebo-controlled study (ISRCTN24203769) to assess the effectiveness of low-level laser therapy (LLLT) in patients with meniscal pathology, including only symptomatic patients with tiny focus of grade 3 attenuation (seen only on 0.7 thickness sequences) or intrasubstance tears with spot of grade 3 signal intensity approaching the articular surface. None of the patients in the study group underwent arthroscopy or new magnetic resonance imaging investigation. Paired-samples t test was used to detect significant changes in subjective knee pain over the experimental period within groups, and ANOVA was used to detect any significant differences between the two groups. Pain was significantly improved for the LLLT group than for the placebo group (F = 154, p < 0.0001). Pain scores were significantly better after LLLT. Four (12.5 %) patients did not respond to LLLT. At baseline, the average Lysholm score was 77 ± 4.6 for the LLLT group and 77.2 ± 2.6 for the placebo group (p > 0.05). Four weeks after LLLT or placebo therapy, the laser group reported an average Lysholm score of 82.5 ± 4.6, and the placebo group scored 79.0 ± 1.9. At 6 months, the laser group had an average Lysholm score of 82.2 ± 5.7, and after 1 year, they scored 81.6 ± 6.6 (F = 14.82923, p = 0.002). Treatment with LLLT was associated with a significant decrease of symptoms compared to the placebo group: it should be considered in patients with meniscal tears who do not wish to undergo surgery.

[The estimation of the efficacy of galvanic peloid therapy for the treatment of the children with chronic post-traumatic knee-joint synovitis following arthroscopy].

The present study has demonstrated that the children suffering from chronic post-traumatic knee-joint synovitis after arthroscopy develop an aseptic inflammatory process in the joints associated with the disturbances of local microcirculation, manifestations of sclerosis and fibrosis in the articular soft tissues. An algorithm for the treatment of synovitis in the postoperative period with the use of galvanic muds has been developed. The estimation of the clinical efficacy of this physiotherapeutic method was performed based on the results of routine medical examination, dynamic ultrasound investigation, and dynamic computed termography.

Effect of He-Ne laser radiation on healing of osteochondral defect in rabbit: a histological study.

This study examined the influence of low-level laser therapy (LLLT) on the healing of a large osteochondral defect in rabbits.An osteochondral defect with 5 mm diameter was surgically induced in the right femoral patellar groove of 48 adult male rabbits. They were divided into a control and an experimental group. The rabbits were treated at 2, 4, 8, and 16 weeks after surgery, with six rabbits in each study period being tested at each biweekly period. The experimental group received LLLT with a helium-neon (He-Ne) laser (632.8 nm, 10 mW) of 148.4 J/cm(2) three times a week, and the control group received placebo LLLT with equipment switched off. The defects were examined macroscopically and microscopically. The results of the histological examination 2 weeks after surgery showed that the osteochondral healing of the control group was significantly accelerated compared with that of the experimental group. However, the osteochondral healing of the experimental group 4 weeks and 16 weeks after surgery showed that healing accelerated significantly compared with that of the control group. The conclusion was that LLLT with an He-Ne laser could not significantly accelerate healing of a large osteochondral defect in rabbits of the experimental group compared with that of the control group throughout the duration of the present study.

Lipid peroxidation, glutathione, vitamin E, and antioxidant enzymes in synovial fluid from patients with osteoarthritis.

AIM: To compare levels of lipid peroxidation and antioxidants in synovial fluid from primary knee osteoarthritis (OA) patients with severe cartilage damage undergoing total knee replacement with those in the synovial fluid from injured knee joint patients with intact cartilage undergoing knee arthroscopy. METHODS: Thirty-two OA patients and 10 injured knee joint patients were recruited. Lipid peroxidation (thiobarbituric acid reactive substances [TBARs]), iron and glutathione (GSH) were measured using a colorimetric method. Vitamin E was measured with high-performance liquid chromatography (HPLC). Activities of antioxidant enzymes (glutathione peroxidase [GPx], superoxide dismutase [SOD]) were analyzed with the use of a kinetic method. RESULTS: TBARs, iron and GSH levels in synovial fluid were not significantly different between OA patients and injured knee joint patients. Antioxidant enzymes such as GPx and SOD activities also indicated no significant difference. Only vitamin E level was significantly lower in the synovial fluid of OA patients than in that of the injured knee joint patients. CONCLUSIONS: Oxidative stress may have a role in pathogenesis of knee osteoarthritis. Vitamin E supplementation may have a role in the management of patients.

BMP-7 protects against progression of cartilage degeneration after impact injury.

In vivo studies were used to characterize a model of cartilage injury leading to osteoarthritis progression in the medial femorotibial joint of sheep. In three subsequent studies, bilateral impact injuries were created and one joint received intraarticular injections of 340 microg of rhBMP-7 protein in a collagen particle carrier while the contralateral knee received the vehicle alone. Sheep were allocated to three groups that received intraarticular injections on day 0 (group A), 21 (group B), or 90 (group C) after experimental knee injury. In each group the, joints were evaluated for signs of osteoarthritis progression 90 days after the last treatment using India ink stained area, OARSI histological scoring, cartilage sGAG content, immunostaining for apoptosis (TUNEL), caspase-3, collagen degradation (Col 2 3/4C short collagen epitope), and the endogenous (pro-) form of BMP-7 protein. Knee joints that received rhBMP-7 immediately after injury had small focal lesions at the injury site that did not progress into the surrounding cartilage. Joints that received BMP-7 3 weeks after injury were improved and had limited progression compared to controls, but joints that received the protein 12 weeks after injury had no statistically significant improvement. These studies suggest that BMP-7 may be chondroprotective after traumatic injury in patients if it is administered within 3 to 4 weeks of the index injury. The mechanism of protection after sublethal injury appeared to be an increased survival of chondrocytes that are able to participate in the repair process.

Oxidant and anti-oxidant systems of synovial fluid from patients with knee post-traumatic arthritis.

It has been suggested that patients with knee post-traumatic arthritis (PA), associated or not to haemarthrosis (HA), display altered oxidant and anti-oxidant systems in their synovial fluid. This study aimed to establish whether this is really the case. Synovial fluid samples were obtained by transdermal arthrocentesis from 69 patients with PA (36 of them had HA) and 22 control subjects. The activities of synovial fluid zinc-copper superoxide dismutase (ZnCuSOD) and manganese superoxide dismutase (MnSOD) isoenzymes, catalase (CAT), glutathione peroxidase (GPX), glutathione reductase (GR) and glutathione-S-transferase (GST) enzymes, and malondialdehyde (MDA) concentration and synovial fluid viscosity were measured in the study groups. Patients with PA had significantly increased activities of all antioxidant enzymes, except CAT, and MDA concentration than did the controls. However, synovial fluid viscosity was found to be decreased in the study group, mainly in the HA subgroup. Results suggest that excessive free radicals production may exist in synovial fluid of PA patients and may contribute to knee joint destruction.

Release of GABA and activation of GABA(A) in the spinal cord mediates the effects of TENS in rats.

Transcutaneous electrical nerve stimulation (TENS) is a commonly utilized non-pharmacological, non-invasive treatment for pain. GABA is a neurotransmitter in the dorsal horn of the spinal cord that mediates analgesia locally, and also through activation of supraspinal sites. TENS reduces hyperalgesia through activation of receptor-mediated pathways at the level of the spinal cord, and supraspinally. The current study tested the hypothesis that either high or low frequency TENS applied to the inflamed knee joint increases GABA in the spinal cord dorsal horn and activates GABA receptors spinally. We utilized microdialysis to sample the extracellular fluid before, during and after TENS and analyzed GABA in dialysates with high performance liquid chromatography. We analyzed the extracellular GABA concentrations in animals with and without knee joint inflammation induced by intra-articular injection of kaolin and carrageenan. We further tested if spinal blockade of GABA receptors prevents the antihyperalgesia produced by TENS in rats with joint inflammation. We show that high frequency TENS increases extracellular GABA concentrations in the spinal cord in animals with and without joint inflammation. The increases in GABA do not occur in response to low frequency TENS, and there are no increases in glycine in response to low or high frequency TENS. However, the reduction in primary hyperalgesia by both high and low frequency TENS is prevented by spinal blockade of GABA(A) receptors with bicuculline. Thus, high frequency TENS increases release of GABA in the deep dorsal horn of the spinal cord, and both high and low frequency TENS reduce primary hyperalgesia by activation of GABA(A) receptors spinally.

Radiographic knee dimensions in discoid lateral meniscus: comparison with normal control.

We reviewed the knee radiographs of 68 cases of arthroscopically proven discoid lateral meniscus, including 42 cases of complete type and 26 cases of incomplete type discoid lateral meniscus. Knee radiographs of 70 cases that had no arthroscopic evidence of pathology of the meniscus were used as controls. We excluded patients who had significant trauma history and who were under 16 years of age or over 60 years to avoid measuring radiographs of skeletally immature or degenerative knees. The absolute values and relative normalized values of specific knee dimensions, such as a squared-off appearance of the lateral femoral condyle, widened femorotibial joint space, cupping of the lateral tibial plateau, obliquity of the lateral tibial plateau articular surface, high fibular head, and hypoplasia of the lateral intercondylar spine, were compared between the patients with discoid lateral meniscus and the normal controls. Among those dimensions, high fibular head and widened lateral tibiofemoral joint space showed statistically significant differences between the discoid lateral meniscus group and normal control group. We suggest that these findings would be useful in screening lateral discoid meniscus on plain radiography.

Crystal deposition in normal and diseased articular cartilage: an extended report.

Particles observed on the surfaces of human articular cartilage following trauma and from chondromalacic, osteoarthritic and rheumatoid joints using the scanning electron microscope were analysed by x-ray diffraction technique. The particles contained calcium and phosphorus and they were identified only in structurally abnormal cartilage. These findings suggest that local abnormality of articular cartilage probably underlies crystal-deposition.

Office arthroscopy: a diagnostic alternative.

Twenty patients with enigmatic knee symptoms were selected for evaluation by both magnetic resonance imaging (MRI) and office arthroscopy. Office arthroscopy was performed in a standard examination room using a miniature (1.7 mm) fiberoptic arthroscope under local anesthesia. All MRI scans were performed on a state-of-the-art 1.5-T magnet unit, and included specialized cartilage sequences in 7 patients. In 14 patients, 26 areas showed articular cartilage changes by arthroscopy (grade 2-3). Only nine of these areas were detected by MRI (sensitivity 34.6%). There were five false-positive and four false-negative readings of meniscal tears by MRI as compared with office arthroscopy. These results improved when postoperative menisci were excluded. Only one of three anterior cruciate ligament (ACL) disruptions identified by MRI could be verified by arthroscopy. The one posterior cruciate ligament (PCL) disruption was confirmed by both techniques. MRI was superior to arthroscopy in identifying bone contusions, subchondral sclerosis, and medial cruciate ligament (MCL) sprains. Office arthroscopy is an accurate and cost-efficient alternative to MRI in diagnostic evaluation of knee pathology in patients with enigmatic symptomatology.