Evaluation of Chondroprotective Activity of Channa striatus in Rabbit Osteoarthritis Model.

OBJECTIVES: The objective of the study is to evaluate the chondroprotective activity of Channa striatus (Channa) and glucosamine sulphate (glucosamine) on histomorphometric examinations, serum biomarker, and inflammatory mediators in experimental osteoarthritis (OA) rabbit model. DESIGN: Anterior cruciate ligament transection (ACLT) was performed to induce OA in thirty-three male New Zealand white rabbits and were randomly divided into three groups: Channa, glucosamine, and control group. The control group received drinking water and the Channa and glucosamine groups were orally administered with 51.4 mg/kg of Channa extract and 77.5 mg/kg of glucosamine sulphate in drinking water, respectively, for eight weeks and then sacrificed. The articular cartilage was evaluated macroscopically and histologically using semiquantitative and quantitative methods. Serum cartilage oligomeric matric protein (COMP), cyclooxygenase 2 (COX-2) enzyme, and prostaglandin E2 (PGE2) were also determined. RESULTS: Macroscopic analysis revealed that Channa group have a significantly lower severity grade of total macroscopic score compared to the control (p < 0.001) and glucosamine (p < 0.05) groups. Semiquantitative histology scoring showed that both Channa and glucosamine groups had lower severity grading of total histology score compared to the control group (p < 0.001). In comparison with the control, Channa group had lower histopathological changes in three compartments of the joint compared to glucosamine group which had lower histological scoring in two compartments only. The cartilage thickness, area, and roughness of both Channa (p < 0.05) and glucosamine (p < 0.05) groups were superior compared to the control group. However, the Channa group demonstrated significantly less cartilage roughness compared to the glucosamine group (p < 0.05). Serum COMP levels were lower in both Channa (p < 0.05) and glucosamine (p < 0.05) groups compared to the control group. CONCLUSION: Both oral administration of Channa extract and glucosamine exhibited chondroprotective action on an ACLT OA-induced rabbit model. However, Channa was superior to glucosamine in maintaining the structure of the cartilage.

Oral shea nut oil triterpene concentrate supplement ameliorates pain and histological assessment of articular cartilage deterioration in an ACLT injured rat knee osteoarthritis model.

Osteoarthritis (OA) is a multifactorial joint disease and a common disabling condition in the elderly population. The associated pain and pathohistological changes in cartilage are common features of OA in both humans and animal models. Shea nut oil extract (SheaFlex75) contains a high triterpenoid concentration and has demonstrated anti-inflammatory and antiarthritic effects in both human and animal studies. In this study, we aim to investigate the potential of SheaFlex75 to prevent articular cartilage deterioration in a rat model of chronic OA progression. By employing anterior cruciate ligament transection (ACLT) with medial meniscectomy (MMx)-induced OA, we found attenuation of both early and chronic onset OA pain and cartilage degeneration in ACLT+MMx rats receiving SheaFlex75 dietary supplementation. Under long-term oral administration, the rats with induced OA presented sustained protection of both pain and OA cartilage integrity compared to the OA-control rats. Moreover, rats subjected to long-term SheaFlex75 ingestion showed normal biochemical profiles (AST, BUN and total cholesterol) and presented relatively lower triglycerides (TGs) and body weights than the OA-control rats, which suggested the safety of prolonged use of this oil extract. Based on the present evidence, preventive management is advised to delay/prevent onset and progression in OA patients. Therefore, we suggest that SheaFlex75 may be an effective management strategy for symptom relief and cartilage protection in patients with both acute and chronic OA.

A hyaluronic acid binding peptide-polymer system for treating osteoarthritis.

Hyaluronic acid (HA) is found naturally in synovial fluid and is utilized therapeutically to treat osteoarthritis (OA). Here, we employed a peptide-polymer cartilage coating platform to localize HA to the cartilage surface for the purpose of treating post traumatic osteoarthritis. The objective of this study was to increase efficacy of the peptide-polymer platform in reducing OA progression in a mouse model of post-traumatic OA without exogenous HA supplementation. The peptide-polymer is composed of an HA-binding peptide (HABP) conjugated to a heterobifunctional poly (ethylene glycol) (PEG) chain and a collagen binding peptide (COLBP). We created a library of different peptide-polymers and characterized their HA binding properties in vitro using quartz crystal microbalance (QCM-D) and isothermal calorimetry (ITC). The peptide polymers were further tested in vivo in an anterior cruciate ligament transection (ACLT) murine model of post traumatic OA. The peptide-polymer with the highest affinity to HA as tested by QCM-D (∼4-fold greater binding compared to other peptides tested) and by ITC (∼3.8-fold) was HABP2-8-arm PEG-COLBP. Biotin tagging demonstrated that HABP2-8-arm PEG-COLBP localizes to both cartilage defects and synovium. In vivo, HABP2-8-arm PEG-COLBP treatment and the clinical HA comparator Orthovisc lowered levels of inflammatory genes including IL-6, IL-1B, and MMP13 compared to saline treated animals and increased aggrecan expression in young mice. HABP2-8-arm PEG-COLBP and Orthovisc also reduced pain as measured by incapacitance and hotplate testing. Cartilage degeneration as measured by OARSI scoring was also reduced by HABP2-8-arm PEG-COLBP and Orthovisc. In aged mice, HABP2-8-arm PEG-COLBP therapeutic efficacy was similar to its efficacy in young mice, but Orthovisc was less efficacious and did not significantly improve OARSI scoring. These results demonstrate that HABP2-8-arm PEG-COLBP is effective at reducing PTOA progression.

Mechanism of Activating the Proprioceptive NT-3/TrkC Signalling Pathway by Reverse Intervention for the Anterior Cruciate Ligament-Hamstring Reflex Arc with Electroacupuncture.

The anterior cruciate ligament (ACL) is an important structure maintaining stability of the knee joints. Deficits in physical stability and the proprioceptive capabilities of the knee joints are observed, when the ACL is damaged. Additionally, a unilateral ACL injury can affect bilateral knee proprioception; therefore, proprioception of the ACL may play a key role in stability. Electroacupuncture therapy has a definite effect nerve regeneration. In this study, cynomolgus monkeys were randomly divided into 4 groups: the model control group, intervention of the injured knee with electroacupuncture (IIKE) group, intervention of the bilateral knees with electroacupuncture (IBKE) group, and the blank control group. The unilateral ACL injury model was developed in IIKE and IBKE groups; acupuncture points around the knees underwent intervention similarly in the IIKE and IBKE groups. Then, mRNA and protein expressions of NT-3 and TrkC in the dorsal root ganglion and of growth-associated protein-43 in the ACL increased according to reverse-transcription quantitative polymerase chain reaction and Western blotting results. Decreased incubations and increased amplitudes were found for somatosensory-evoked potentials and motor nerve conduction velocity. The finding indicates that electroacupuncture may play an important role in the recovery of proprioception in the ACL by activating the NT-3/TrkC signalling pathway.

Inhibition of cartilage degradation and suppression of PGE2 and MMPs expression by pomegranate fruit extract in a model of posttraumatic osteoarthritis.

OBJECTIVE: Osteoarthritis (OA) is characterized by cartilage degradation in the affected joints. Pomegranate fruit extract (PFE) inhibits cartilage degradation in vitro. The aim of this study was to determine whether oral consumption of PFE inhibits disease progression in rabbits with surgically induced OA. METHODS: OA was surgically induced in the tibiofemoral joints of adult New Zealand White rabbits. In one group, animals were fed PFE in water for 8 wk postsurgery. In the second group, animals were fed PFE for 2 wk before surgery and for 8 wk postsurgery. Histologic assessment and scoring of the cartilage was per Osteoarthritis Research Society International guidelines. Gene expression and matrix metalloproteinases (MMP) activity were determined using quantitative reverse transcriptase polymerase chain reaction and fluorometric assay, respectively. Interleukin (IL)-1 ß, MMP-13, IL-6, prostaglandin (PG)E2, and type II collagen (COL2A1) levels in synovial fluid/plasma/culture media were quantified using enzyme-linked immunosorbent assay. Expression of active caspase-3 and poly (ADP-ribose) polymerase p85 was determined by immunohistochemistry. Effect of PFE and inhibitors of MMP-13, mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB was studied in IL-1 ß-stimulated rabbit articular chondrocytes. RESULTS: Safranin-O-staining and chondrocyte cluster formation was significantly reduced in the anterior cruciate ligament transaction plus PFE fed groups. Expression of MMP-3, MMP-9, and MMP-13 mRNA was higher in the cartilage of rabbits given water alone but was significantly lower in the animals fed PFE. PFE-fed rabbits had lower IL-6, MMP-13, and PGE2 levels in the synovial fluid and plasma, respectively, and showed higher expression of aggrecan and COL2A1 mRNA. Significantly higher numbers of chondrocytes were positive for markers of apoptosis in the joints of rabbits with OA given water only compared with those in the PFE-fed groups. PFE pretreatment significantly reduced IL-1 ß induced IL-6 and MMPs expression in rabbit articular chondrocytes. These effects were also mimicked using MMP-13, MAPK, and NF-κB inhibitors in IL-1 ß-stimulated rabbit chondrocytes. In an in vitro activity assay, PFE blocked the activity of MMP-13. Like MAPK and NF-κB inhibitors, PFE was also effective in inhibiting IL-1 ß-induced PGE2 production in rabbit chondrocytes. PFE also reversed the inhibitory effect of IL-1ß on COL2A1 mRNA and protein expression in IL-1 ß-stimulated rabbit chondrocytes. CONCLUSION: The present data highlight the chondroprotective effects of PFE oral consumption in a model of posttraumatic OA and suggest that PFE-derived compounds may have potential value in the management of OA.

Morus alba L. Stem Extract Attenuates Pain and Articular Cartilage Damage in the Anterior Cruciate Ligament Transection-Induced Rat Model of Osteoarthritis.

AIM: This study was designed to investigate the anti-nociceptive effect of Morus alba stem extract as well as its cartilage protective effect in the anterior cruciate ligament transection (ACLT)-induced rat model of osteoarthritis (OA). METHODS: The anti-nociceptive effect of this plant extract was determined by measuring hind limb weight bearing, while the severity of cartilage damage to the knee joints was evaluated using the modified Mankin grading system. RESULTS: Oral administration of M. alba stem extract (56 and 560 mg/kg) significantly attenuated joint pain as indicated by a significant (p < 0.05) increase in the values of percent weight borne on the operated hind limb for the OA-induced groups that received M. alba stem extract at 56 and 560 mg/kg when compared to those of the vehicle-treated OA-induced group. In addition, a significant improvement in the Mankin score was also observed in rats treated with 560 mg/kg M. alba stem extract, which was in agreement with its pain-relieving effect. CONCLUSION: The results showed that M. alba stem extract exhibited an anti-nociceptive effect as well as cartilage protection in the ACLT-induced rat model of OA, supporting its potential use as a therapeutic treatment for OA.

Electroacupuncture protects against articular cartilage erosion by inhibiting mitogen-activated protein kinases in a rat model of osteoarthritis.

OBJECTIVE: The therapeutic effects of electroacupuncture (EA) on osteoarthritis (OA) are well documented; however, the precise mechanisms of action have not yet been fully elucidated. The present study aimed to investigate the effect of EA on cartilage in an experimental animal model of OA induced by anterior cruciate ligament transection (ACLT) and to examine for concomitant changes in the expression of mitogen-activated protein kinases (MAPKs) in the articular cartilage. METHODS: Thirty-three-month-old male Sprague Dawley rats were randomly divided into the following three groups (n=10 each): sham operated group (Control group), ACLT without treatment (ACLT group), and ACLT with EA treatment (ACLT+EA group). One week after ACLT, rats in the ACLT+EA group received 12 weeks of EA treatment. Histological analysis and quantitative real-time PCR were used to investigate the effects of EA on cartilage morphology (quantified using modified Mankin scores) and expression of MAPKs (p38, c-Jun N-terminal kinase (c-Jun), and extracellular signal-regulated kinase (ERK)1), respectively. RESULTS: ACLT produced coarse cartilage surfaces, fibrous degeneration, and fissuring, all of which were suppressed by EA treatment. Although Mankin scores in the ACLT+EA group were significantly higher compared to the Control group (p<0.01), they were significantly lower than the (untreated) ACLT group (p<0.01). The increase in mRNA expression of p38, c-Jun, ERK1, and matrix metalloproteinase (MMP)-13 observed in cartilage after ACLT was significantly inhibited by EA. CONCLUSIONS: EA appears to prevent the degeneration of articular cartilage, at least partly through regulation of MMP-13 and inhibition of MAPKs in the cartilage of rats with ACLT-induced OA.

Low-level laser therapy prevents degenerative morphological changes in an experimental model of anterior cruciate ligament transection in rats.

The aim of this study was to analyze the effects of low-level laser therapy (LLLT) on the prevention of cartilage damage after the anterior cruciate ligament transection (ACLT) in knees of rats. Thirty male rats (Wistar) were distributed into three groups (n = 10 each): injured control group (CG); injured laser-treated group at 10 J/cm(2) (L10), and injured laser-treated group at 50 J/cm(2) (L50). Laser treatment started immediately after the surgery and it was performed for 15 sessions. An 808 nm laser, at 10 and 50 J/cm(2), was used. To evaluate the effects of LLLT, the qualitative and semi-quantitative histological, morphometric, and immunohistochemistry analysis were performed. Initial signs of tissue degradation were observed in CG. Interestingly, laser-treated animals presented a better tissue organization, especially at the fluence of 10 J/cm(2). Furthermore, laser phototherapy was able of modulating some of the aspects related to the degenerative process, such as the prevention of proteoglycans loss and the increase in cartilage area. However, LLLT was not able of modulating chondrocytes proliferation and the immunoexpression of markers related to inflammatory process (IL-1 and MMP-13). This study showed that 808 nm laser, at both fluences, prevented features related to the articular degenerative process in the knees of rats after ACLT.

Twin athlete brothers with open physes operated for ACL reconstruction on the same day, but with different elapsed times after injury: a 5-year follow-up.

We present the case of twin brothers with open physes who practiced judo to a high level and were operated on the same day for anterior cruciate ligament reconstruction. One of them was injured a year before surgery, and the other was injured a month before the procedure. The brother who chose to undergo a conservative treatment sustained meniscus injury afterwards and showed lower objective results when evaluated 5 years after surgery.

[Pulsed electromagnetic field therapy inhibits chondrocyte apoptosis in rabbits with osteoarthritis].

OBJECTIVE: To determine the effect of pulsed electromagnetic field (PEMF) treatment on chondrocyte morphology, chondrocyte apoptosis, and the expression of apoptosis related proteins in rabbits. METHODS: 24 white New Zealand rabbits were randomly divided into three groups: normal control group (NC group), anterior cruciate ligament transection without treatment (ACLT group), and anterior cruciate ligament transection with pulsed electromagnetic field treatment (PEMF group). Six weeks after anterior cruciate ligament transection, the rabbits in the PEMF group were given 2 weeks of pulsed electromagnetic field treatment. RESULTS: Rabbits in the PEMF group had significantly lower Mankin scores than those in the ACLT group, although the scores were higher than that of the NC group. The rabbits in the PEMF groups also had significantly lower levels of apoptosis index of chondrocytes and expression of caspase-3 compared with those in the ACLT group. The expression of caspase-8 in the rabbits in the PEMF group was higher compared to the NC group, but no significant difference compared with that of the ACLT group. CONCLUSION: Pulsed electromagnetic field treatment has therapeutic effect on the experimental osteoarthritis, which is likely a result of inhibition of apoptosis in chondrocytes.

Effects of phototherapy on cartilage structure and inflammatory markers in an experimental model of osteoarthritis.

The aim of this study was to evaluate the effects of laser phototherapy on the degenerative modifications on the articular cartilage after the anterior cruciate ligament transection (ACLT) in the knee of rats. Eighty male rats (Wistar) were distributed into four groups: intact control group (IG), injured control group (CG), injured laser treated group at 10 J/cm(2) (L10), and injured laser treated group at 50 J/cm(2) (L50). Animals were distributed into two subgroups, sacrificed in 5 and 8 weeks postsurgery. The ACLT was used to induce knee osteoarthritis in rats. After 2 weeks postsurgery, laser phototherapy initiated and it was performed for 15 and 30 sessions. The histological findings revealed that laser irradiation, especially at 10 J/cm(2), modulated the progression of the degenerative process, showing a better cartilage structure and lower number of condrocytes compared to the other groups. Laser phototherapy was not able to decrease the degenerative process measured by Mankin score and prevent the increase of cartilage thickness related to the degenerative process. Moreover, it did not have any effect in the biomodulation of the expression of markers IL1ß, tumor necrosis factor-α, and metalloprotein-13. Furthermore, laser irradiated animals, at 50 J/cm(2) showed a lower amount of collagen type 1.

Anti-inflammatory response of dietary vitamin E and its effects on pain and joint structures during early stages of surgically induced osteoarthritis in dogs.

There is evidence that vitamin E (VE) has anti-inflammatory and analgesic properties in human osteoarthritis (OA). This double-blinded and randomized pilot study used a broad spectrum of clinical and laboratory parameters to investigate whether such beneficial effects could be detected in a canine experimental OA model. Dogs were divided into 2 groups: control (n = 8), which received a placebo, and test group (n = 7), which received 400 IU/animal per day of VE for 55 d, starting the day after transection of the cranial cruciate ligament. Lameness and pain were assessed using a visual analogue scale (VAS), numerical rating scale (NRS), and electrodermal activity (EDA) at day 0, day 28, and day 55. Cartilage and synovial inflammation lesions were assessed. One-side comparison was conducted at an alpha-threshold of 10%. At day 56, dogs were euthanized and concentrations of prostaglandin E2 (PGE2), nitrogen oxides (NOx), and interleukin-1 beta (IL-1ß) were measured in synovial fluid. Concentrations of NOx and PGE2 in synovial fluid were lower in the test group (P < 0.0001 and P = 0.03, respectively). Values of VAS, NRS, and EDA showed a consistent trend to be lower in the test group than in the control, while statistical significance was reached for VAS at day 55 and for EDA at day 28 (adjusted P = 0.07 in both cases). Histological analyses of cartilage showed a significant reduction in the scores of lesions in the test group. This is the first time that a study in dogs with OA using a supplement with a high dose of vitamin E showed a reduction in inflammation joint markers and histological expression, as well as a trend to improving signs of pain.

La vitamine E (VE) est connue par ses propriétés anti-inflammatoires et analgésiques dans le traitement de l'ostéoarthrose (OA) chez l'humain. Dans notre étude pilote nous avons utilisé un ensemble de paramètres cliniques et de laboratoire afin de déterminer si ces effets bénéfiques de la VE pourront être détectés chez le chien arthrosique, dans un modèle expérimental d'OA. Les chiens utilisés ont été divisés en 2 groupes: témoin (n = 8), qui a reçu un placebo et un groupe supplémenté (n = 7), qui a reçu 400 UI de VE/animal/jour pendant 55 jours, la supplémentation orale a commencé un jour après la section du ligament croisé crânial. Avant la chirurgie (J0), J28 et J55 après chirurgie, la boiterie et la douleur ont été évaluées à l'aide d'une échelle visuelle analogique (EVA), d'une échelle d'évaluation numérique (NRS), et par la mesure de l'activité électrodermique (EDA). Les lésions au niveau du cartilage et l'inflammation synoviale ont été évalués. Une seule comparaison statistique a été réalisée avec un seuil alpha à 10 %. Au jour 56, les chiens ont été euthanasiés et les concentrations de prostaglandine E2 (PGE2), d'oxyde d'azote (NOx) et d'interleukine-1 bêta (IL-1ß) ont été mesurées dans le liquide synovial. Les concentrations synoviales de NOx et de PGE2 étaient plus faibles dans le groupe traité (P < 0,0001 et P = 0,03, respectivement). Les valeurs de l'EVA, de NRS et de l'EDA ont montré une tendance constante à être plus faible dans le groupe traité par comparaison au groupe témoin, avec un effet significatif de la VE qui a été observé pour VAS au jour 55 et EDA au jour 28 (P ajustée = 0,07 dans les deux cas). Les analyses histologiques du cartilage ont montré une réduction significative des scores lésionnels chez le groupe traité. Cette étude est la première à démontrer qu'une supplémentation orale avec une dose élevée de VE chez des chiens arthrosiques permet de réduire la libération des marqueurs inflammatoires et les lésions histologiques au niveau du cartilage, ainsi qu'une tendance à améliorer les signes de douleur.(Traduit par Docteur Serge Messier).

Short-term effects of radiofrequency shrinkage treatment for anterior cruciate ligament relaxation on proprioception.

OBJECTIVE: Radiofrequency (RF) shrinkage is used in anterior cruciate ligament (ACL) reconstruction. The present study investigated the therapeutic effects of RF on ACL relaxation and the probable influencing factors. METHODS: Patients with ACL relaxation were included. Participants were randomly divided into two groups: a treatment group, in which patients were treated with RF shrinkage (RF group); a control group, in which patients received conventional surgical treatment. Thermal shrinkage was performed on ACL using an ArthroCare® CAPSure® wand. Lysholm scores, proprioceptive testing and Tegner activity scores were evaluated before and after treatment (at 6 and 12 months). RESULTS: A total of 38 patients were included. The mean ± SD Lysholm score of those in the RF group at 12 months' post-treatment was significantly higher than in controls. The angle of deviation of the knee joint in RF group was significantly larger than in the control group at 6 months' post-treatment. CONCLUSIONS: RF shrinkage treatment for ACL laxity could improve knee scores, and may affect proprioception and recovery of activity after surgery.

Treatment with SiMiaoFang, an anti-arthritis chinese herbal formula, inhibits cartilage matrix degradation in osteoarthritis rat model.

A Chinese herbal preparation, SiMiaoFang (SMF), has been used clinically for treating arthralgia by virtue of its anti-inflammatory and pain-relieving activities. However, no evidence base links SMF to anti-osteoarthritis (OA), particularly its link to inhibiting cartilage matrix degradation. In this study, we undertook a characterization of anti-OA activity of SMF using an in vivo rat model induced by anterior cruciate ligament transection and medial meniscus resection (ACLT+MMx) together with in vitro studies with chondrocytes for further molecular characterization. ACLT+MMx rats were treated with SMF at doses of 0.63, 1.25, and 2.5 grams/kg per day for 6 weeks. SMF treatments significantly inhibited cartilage matrix degradation, as indicated by increasing proteoglycan and collagen content, particularly type II collagen expression in articular cartilage, decreasing CTX-II (collagen type II degradation marker), and increasing CPII (collagen type II synthesis marker) in circulation. Moreover, SMF suppressed synovial inflammation and inhibited release of interleukin-1ß (IL-1ß) and tumor necrosis factor-α in serum. The levels of serum prostaglandin E2 and nitric oxide productions were decreased via suppression of the production of cyclooxygenase-2 and inducible nitric oxide synthase, respectively. Importantly, SMF interfered with OA-augmented expression of matrix metalloproteinases (MMPs) -3 and -13 and aggrecanases (ADAMTS) -4 and -5, which are considered to be key enzymes in cartilage matrix degradation, and simultaneously augmented OA-reduced tissue inhibitors of metalloproteinases (TIMPs) -1 and -3 expression in the joints. The largest changes in these parameters were found at the highest dose. Meanwhile, SMF significantly decreased MMP-3 and -13 and increased TIMP-1 and -3 at mRNA and protein levels in IL-1ß-induced chondrocytes. These findings provide the first evidence that SMF effectively treats OA by inhibiting cartilage matrix degradation.

"Hybrid exercise" prevents muscle atrophy in association with a distinct gene expression pattern.

"Hybrid exercise" utilizing combined electrical stimulation and voluntary muscle contraction has been developed as a muscle exercise method. Although our previous studies have confirmed the effectiveness of the procedure, the mechanisms of its efficacy still remain unclear. In the present study, we identified genes that are specifically expressed in disused muscles, using the semitendinosus muscle from patients who underwent anterior cruciate ligament (ACL) reconstruction. Preoperative exercise was performed by four ACL-injured patients, who were subjected either to hybrid exercise (n=2), electrical stimulation (n=1), or no electrical stimulation (n=1), in addition to standard weight training for 4 weeks. Cross-sectional area (CSA) of the semitendinosus muscle was measured before and after the exercise by magnetic resonance imaging (MRI). A piece of the semitendinosus muscle was isolated during the surgery, and comprehensive analysis of the gene expression in this sample was performed using DNA microarray analysis. CSA increased in size by 4.2 and 14.7%, respectively, after hybrid exercise, and by 1.4% after electrical stimulation. However it shrunk by 7.7% without electrical stimulation. DNA microarray analysis revealed that hybrid exercise was more effective at stimulating the expression of signal transduction-, transcription- and cytoskeleton-related genes in semitendinosus muscles than electrical stimulation alone. In particular, gene ontology analysis revealed that hybrid exercise induced significantly higher expression of eukaryotic translation initiation factor 5A (EIFSA), peroxisomal biogenesis factor 6 (PEX6) and histone cluster 1 H4 (HIST1H4), compared with electrical stimulation alone. The expression of signal transduction-, transcription- and cytoskeleton-related genes may play an important role in muscle bulk increasing mechanisms in hybrid exercise.

Effect of light-emitting diode (LED) therapy on the development of osteoarthritis (OA) in a rabbit model.

OBJECTIVE: The objective of this study was to evaluate whether light-emitting diodes (LEDs) could be effective in a noninvasive, therapeutic device for the treatment of osteoarthritic (OA) knee joints. DESIGN: Five weeks following the anterior cruciate ligament transection (ACLT) of mature New Zealand White rabbits, the animal knees were exposed to LED stimulation at intervals of 10 min/day, 5 days/week for 5 weeks in the experimental group (n=7). The device used high intensity red and infrared (IR) LEDs with a total amount of energy delivered to the skin of 2.4 J/cm(2). Animals were sacrificed at 9 weeks postoperatively. Femoral surface gross morphology was evaluated with a modified Outerbridge classification and mRNA expression of catabolic and anabolic markers from femoral condyle cartilage and synovial tissue was assessed using RT-PCR. A control group was harvested 9 weeks following untreated ACLT. RESULTS: Gross morphometry of the control group showed four Grade II, two Grade III and one Grade IV (average 2.6) condyles macroscopically. The experimental group showed two Grade I and five Grade II (average 1.7) (Table 1). mRNA expression of aggrecan in the cartilage showed no difference between the groups, however type II collagen expression increased in the experimental group compared with control. TNF-α expression was significantly decreased in the experimental group compared to control. CONCLUSIONS: There was general preservation of the articular surface and decreased levels of inflammation in the osteoarthritic joints with the application of LED therapy. This may provide potential application as a noninvasive treatment.

Vitamin E and C supplementation does not ameliorate muscle dysfunction after anterior cruciate ligament surgery.

Muscle atrophy and weakness are predominant impairments after anterior cruciate ligament (ACL) surgical repair. We tested the hypothesis that vitamin E and C supplementation will improve recovery from ACL injury. Men undergoing elective ACL surgery were randomly assigned to twice-daily supplements of either antioxidants (AO; vitamins E and C, n=10) or matching placebos (n=10) from 2 weeks before until 3 months after surgery. Each subject provided several fasting blood draws, two muscle biopsies from the thigh muscle of the injured limb, and strength and thigh circumference measurements of the lower limbs. Muscle atrophy was apparent in both groups before and several days after surgery. Compared with baseline measurements, peak isometric force of the injured limb increased significantly (P<0.05) by 3 months postsurgery in both treatment groups; however, AO supplementation did not augment these strength gains. By contrast, baseline plasma ascorbic acid concentrations correlated (r=0.59, P=0.006) with subsequent improvement in the strength of the injured limb. In summary, vitamin E and C supplementation was ineffective in potentiating the improvement in force production by the injured limb; however, baseline vitamin C status was associated with beneficial outcomes in strength, suggesting that long-term dietary habits are more effective than short-term supplements.

Evaluation of pentosan polysulfate sodium in the postoperative recovery from cranial cruciate injury in dogs: a randomized, placebo-controlled clinical trial.

OBJECTIVE: To evaluate the efficacy of pentosan polysulfate (PPS) for improving the recovery period and mitigate the progression of osteoarthritis (OA) of the canine stifle after extracapsular stabilization of cranial cruciate ligament (CCL) injuries. STUDY DESIGN: Randomized, blinded, placebo-controlled clinical trial. ANIMALS: Dogs (n=40) with unilateral CCL instability. METHODS: Each dog had an extracapsular stabilization of the stifle with or without partial meniscectomy. Dogs were divided into 4 groups based on preoperative radiographic assessment and whether a partial meniscectomy was performed. Dogs were randomly assigned to either (3 mg/kg) PPS or placebo treatment in each group, and then injected subcutaneously weekly for 4 weeks. Lameness, radiographic changes, biological marker concentration in blood and urine, and ground reaction forces (GRFs) were collected preoperatively, and at 6, 12, 24, and 48 weeks. Data were analyzed within and between groups using repeated measures ANOVA; P<.05 was considered significant. RESULTS: No adverse reactions to PPS were reported. Thirty-nine dogs completed a minimum of 24-weeks follow-up and 33 dogs completed 48 weeks. All dogs clinically improved after surgery without differences in lameness score, vertical GRFs, or radiographic progression. Grouped and evaluated only by initial radiographic score, PPS-treated dogs improved significantly faster in braking GRFs than placebo-treated dogs. In dogs with partial meniscectomies, urine deoxypyridinoline, and serum carboxy-propeptide of type II collagen were significantly increased at 6 weeks in placebo-treated dogs compared with PPS-treated dogs. CONCLUSIONS: PPS administered after stabilization of the cruciate deficient stifle may prove to be a useful adjunctive treatment option, although further studies are necessary to substantiate this claim.

COL-3 inhibition of collagen fragmentation in ruptured cranial cruciate ligament explants from dogs with stifle arthritis.

Inhibition of collagen fragment generation in canine cranial cruciate ligament (CCL) explant cultures by the matrix metalloprotease inhibitor (6-demethyl)-6-deoxy-4-dedimethylamino tetracycline (COL-3) was studied. Cranial cruciate ligament specimens were collected from dogs with inflammatory stifle arthritis/CCL rupture and dogs with normal stifles. Explant cultures from each CCL specimen included one COL-3 treated explant and a baseline control; explants from 12 ruptured CCLs were prepared in triplicate and a protease inhibitor cocktail positive control was used. Explant supernatants were analyzed for generation of collagen fragments after two days. Treatment of ruptured CCL explants with 10(-4)M COL-3 decreased generation of collagen fragments. The extent of this inhibition was increased in explants treated with a protease inhibitor cocktail. Generation of collagen fragments was increased in ruptured CCLs, when compared with intact CCLs. It is concluded that generation of collagen fragments was increased in pathological ruptured CCL explants. This degradation could be significantly inhibited in vitro by 10(-4)M COL-3.

[The effect of osteoprotegerin on tendon-bone healing after reconstruction of the anterior cruciate ligament: a histomorphological and radiographical study in the rabbit]. / Der Einfluss von Osteoprotegerin auf die Sehne-zu-Knochen-Heilung nach Rekonstruktion des vorderen Kreuzbandes: Eine histomorphologische und radiographische Studie im Kaninchenmodell.

AIM: Improvement of the bony incorporation of a soft-tissue graft after ACL reconstruction by local administration of Osteoprotegerin between the bone and tendon graft. METHOD: Fifteen New Zealand White rabbits underwent unilateral anterior cruciate ligament (ACL) reconstruction using an autologous semitendinosis tendon graft. We compared the effect of three OPG doses (5 microg, 50 microg, or 100 microg) at the tendon-bone interface to the controls (OPG carrier) and ACL reconstruction only. Specimens were analyzed at 3 weeks using radiology, histology and histomorphometry to investigate the effect of OPG on the bony incorporation of the tendon graft. RESULTS: Animals treated with OPG 100 microg had a significant (p = 0.007) increase in newly-formed bone around the graft compared to the control group (0.16 +/- 0.01 mm(2); 0.06 +/- 0.02 mm(2)). No significant differences were found between the controls and the other groups (tendon graft only, OPG 5 microg, and 50 microg) (p > 0.05). Bone mineral density, measured in image-pixel brightness (IPB; reference range: 0-255), along the edge of the bone tunnel was greater in the OPG 100 microg group (169.5 +/- 5.9 IPB) compared to the control group (150.3 +/- 4.3 IPB) but this was not statistically significant (p = 0.083). There was a significant decrease in the number of osteoclasts per high-power microscopic fields (HPF) lining the bone tunnel in the OPG 100 microg group compared to the control group (4.4 +/- 2.5 cells/HPF; 6.4 +/- 1.8 cells/HPF) (p = 0.022). No significant differences were found between the control group and the other groups in osteoclast numbers (p > 0.05). CONCLUSION: Since tendon-bone healing requires new bone formation and bone ingrowth around a tendon graft, OPG may improve biologic graft fixation. A potential implication could be earlier return to function or better conditions in revision surgery.