Association Between Leg Muscle Thickness and Walking Test with the Haemophilia-Specific Functional Parameters.

OBJECTIVE: To evaluate the muscle thickness and walking test in people with haemophilia A (PWH) and their correlation to joint health and functional impairments. DESIGN: Cross-sectional study. RESULTS: 29 severe/moderate PWH were enrolled. Muscle thickness of quadriceps and medial gastrocnemius were measured using ultrasound. Joint health and functional capacity were assessed using Haemophilia Joint Health Score (HJHS), Haemophilia Early Arthropathy Detection with Ultrasound (HEAD-US), 6-Minute Walking test (6MWT), Haemophilia Quality of Life Questionnaire for Adults (Haem-A-QoL), and Haemophilia Activities List (HAL). Quadriceps muscle thickness significantly correlated with HJHS knee, HEAD-US knee, and HAL. Calf muscle thickness significantly correlated with the HJHS ankle. After adjusted age and BMI, calf muscle thickness was inversely associated with the HJHS ankle. 6MWT was found to significantly correlate with HJHS total, HEAD-US total, Haem-A-QoL, and HAL. CONCLUSION: Muscle thickness and the distance of 6MWT were linked to assessment of joint health, quality of life and activity participation in PWH. Ultrasound measurement of muscle thickness and walking test appear to be useful tools for the assessment of joint health and functional status in PWH.

A Functional Polymorphism Downstream of Vitamin A Regulator Gene CYP26B1 Is Associated with Hand Osteoarthritis.

While genetic analyses have revealed ~100 risk loci associated with osteoarthritis (OA), only eight have been linked to hand OA. Besides, these studies were performed in predominantly European and Caucasian ancestries. Here, we conducted a genome-wide association study in the Han Chinese population to identify genetic variations associated with the disease. We recruited a total of 1136 individuals (n = 420 hand OA-affected; n = 716 unaffected control subjects) of Han Chinese ancestry. We carried out genotyping using Axiom Asia Precisi on Medicine Research Array, and we employed the RegulomeDB database and RoadMap DNase I Hypersensitivity Sites annotations to further narrow down our potential candidate variants. Genetic variants identified were tested in the Geisinger's hand OA cohort selected from the Geisinger MyCode community health initiative (MyCode®). We also performed a luciferase reporter assay to confirm the potential impact of top candidate single-nucleotide polymorphisms (SNPs) on hand OA. We identified six associated SNPs (p-value = 6.76 × 10-7-7.31 × 10-6) clustered at 2p13.2 downstream of the CYP26B1 gene. The strongest association signal identified was rs883313 (p-value = 6.76 × 10-7, odds ratio (OR) = 1.76), followed by rs12713768 (p-value = 1.36 × 10-6, OR = 1.74), near or within the enhancer region closest to the CYP26B1 gene. Our findings showed that the major risk-conferring CC haplotype of SNPs rs12713768 and rs10208040 [strong linkage disequilibrium (LD); D' = 1, r2 = 0.651] drives 18.9% of enhancer expression activity. Our findings highlight that the SNP rs12713768 is associated with susceptibility to and severity of hand OA in the Han Chinese population and that the suggested retinoic acid signaling pathway may play an important role in its pathogenesis.

High-Molecular-Weight Hyaluronic Acid Inhibits IL-1ß-Induced Synovial Inflammation and Macrophage Polarization through the GRP78-NF-κB Signaling Pathway.

Recent evidence has suggested that synovial inflammation and macrophage polarization were involved in the pathogenesis of osteoarthritis (OA). Additionally, high-molecular-weight hyaluronic acid (HMW-HA) was often used clinically to treat OA. GRP78, an endoplasmic reticulum (ER) stress chaperone, was suggested to contribute to the hyperplasia of synovial cells in OA. However, it was still unclear whether HMW-HA affected macrophage polarization through GRP78. Therefore, we aimed to identify the effect of HMW-HA in primary synovial cells and macrophage polarization and to investigate the role of GRP78 signaling. We used IL-1ß to treat primary synoviocytes to mimic OA, and then treated them with HMW-HA. We also collected conditioned medium (CM) to culture THP-1 macrophages and examine the changes in the phenotype. IL-1ß increased the expression of GRP78, NF-κB (p65 phosphorylation), IL-6, and PGE2 in primary synoviocytes, accompanied by an increased macrophage M1/M2 polarization. GRP78 knockdown significantly reversed the expression of IL-1ß-induced GRP78-related downstream molecules and macrophage polarization. HMW-HA with GRP78 knockdown had additive effects in an IL-1ß culture. Finally, the synovial fluid from OA patients revealed significantly decreased IL-6 and PGE2 levels after the HMW-HA treatment. Our study elucidated a new form of signal transduction for HMW-HA-mediated protection against synovial inflammation and macrophage polarization and highlighted the involvement of the GRP78-NF-κB signaling pathway.

Attenuative Effects of Platelet-Rich Plasma on 30 kDa Fibronectin Fragment-Induced MMP-13 Expression Associated with TLR2 Signaling in Osteoarthritic Chondrocytes and Synovial Fibroblasts.

Proteolytic fragments of fibronectin can have catabolic effects on cartilage, menisci, and synovium. Previous studies have reported that Toll-like receptor (TLR) signaling pathways might be associated with joint inflammation and joint destruction. Platelet-rich plasma (PRP) is increasingly being used to treat a range of joint conditions; however, it has yet to be determined whether PRP influences fibronectin fragment (FN-f) procatabolic activity and TLRs. In this study, human primary culture cells were treated with 30 kDa FN-f with/without PRP co-incubation, and then analyzed using real-time PCR to determine gene expression levels in articular chondrocytes, meniscal fibrochondrocytes, and synovial fibroblasts. Protein levels were evaluated by Western immunoblotting. This study observed an increase in the protein expression of matrix metalloproteinases (MMPs), Toll-like receptor 2 (TLR2), nitric oxide synthase 2 (NOS2), prostaglandin-endoperoxide synthase (PTGS2), and cyclooxygenase 2 (COX2) in articular chondrocytes, meniscal fibrochondrocytes, and synovial fibroblasts following insult with 30 kDa FN-f. Upregulation of these genes was significantly attenuated by PRP treatment. TLR2 and matrix metalloproteinase 13 (MMP-13) were also significantly attenuated by cotreatment with 30 kDa FN-f + PRP + TLR2 inhibitor. PRP treatment was shown to attenuate the 30 kDa FN-f-induced MMP-13 expression associated with the decreased expression of TLR2 in osteoarthritic chondrocytes and synovial fibroblasts. PRP treatment was also shown to attenuate procatabolic activity associated with MMP-13 expression via the TLR2 signaling pathway.

Ameliorative Effects of Cardamonin on Monosodium Urate-Induced Gouty Arthritis through Inhibiting NLRP3 Inflammasome Mediation.

Background and Objectives: Gouty arthritis is an acute inflammatory response caused by the precipitation of monosodium urate (MSU) crystals in joints. The triggering of MSU leads to increased production of inflammatory cytokines, such as interleukin-1ß, which in turn lead to the formation of macromolecular complexes, referred to as inflammasomes. Thorough characterization of the NLRP3 inflammasome can be used as an indicator of an immune response against harmful stimuli. Cardamonin is a chalcone, mainly found in the seeds of Alpinia katsumadai, and exhibits anti-inflammatory activity by inhibiting the release of pro-inflammatory cytokines in vitro. However, the mechanism by which cardamonin treatment alleviates gouty arthritis has yet to be fully elucidated. Materials and Methods: In vitro or in vivo models were used to study whether cardamonimn inhibited NLRP3 inflammasome activation or suppressed gouty inflammation. Results: In the current study, we determined that most NLRP3 was released passively after MSU stimulation, and this release of NLRP3 promoted caspase-1 activation and IL-1ß secretion. Cardamonin was shown to decrease both the activity of caspase-1 and secretion of IL-1ß in J774A.1 macrophage cells subjected to MSU stimulation. Cardamonin was also shown to attenuate the production of COX-2 in MSU-stimulated J774A.1 macrophage cells. Finally, cardamonin reduced the thickness of the synovial lining and the infiltration of gouty arthritis in a rat model. Conclusions: Overall, cardamonin significantly attenuated IL-1ß secretion, caspase-1 activity, and COX-2 production stimulated by MSU. These findings provide new insights into the molecular mechanisms underlying the effects of cardamonin treatment for gouty arthritis.

Interleukin-26 Has Synergistic Catabolic Effects with Palmitate in Human Articular Chondrocytes via the TLR4-ERK1/2-c-Jun Signaling Pathway.

The inflammatory cytokine interleukin-26 (IL-26) is highly expressed in the serum and synovial fluid of patients with inflammatory arthritis. The effect of IL-26 on human articular chondrocytes (HACs) remains unclear. Obesity is associated with disability of patients with rheumatoid arthritis and disease activity in those with ankylosing spondylitis. The saturated free fatty acid palmitate with IL-1ß can synergistically induce catabolic effects in HACs. The aim of this study was to evaluate the effects of IL-26 and palmitate in HACs. In this study, palmitate markedly synergizes the IL-26-induced proinflammatory effects and matrix protease, including COX-2, IL-6, and MMP-1, in HACs via the toll-like receptor 4 (TLR4)-ERK1/2-c-Jun signal transduction pathway. The synergistic catabolic effects of palmitate and IL-26 were attenuated by inhibitors of TLR4 (TAK242), ERK1/2 (U0126), or c-Jun (SP600125) in HACs and cartilage matrix. In addition, metformin, a potential inhibitor of TLR4, also decreased expression of COX-2 and IL-6 induced by co-incubation with IL-26 and palmitate. IL-26 and palmitate synergistically induced expression of inflammatory and catabolic mediators, resulting in articular cartilage matrix breakdown. The present study also revealed a possible mechanism and therapeutic targets against articular cartilage degradation by increased saturated fatty acids in patients with inflammatory arthritis.

Cardamonin Attenuates Inflammation and Oxidative Stress in Interleukin-1ß-Stimulated Osteoarthritis Chondrocyte through the Nrf2 Pathway.

Osteoarthritis (OA) is a chronic degenerative joint disease characterized by the deterioration of articular cartilage. The progression of OA leads to an increase in inflammatory mediators in the joints, thereby promoting the destruction of the cartilage matrix. Recent studies have reported on the anti-inflammatory and antioxidant properties of cardamonin, which also appears to interact with cellular targets, such as nuclear erythroid 2-related factor 2 (Nrf2), extracellular signal-regulated kinase (ERK), and mammalian target of rapamycin (mTOR) during the progression of tumors. To date, few studies have investigated the effects of cardamonin on chondrocyte inflammation. In the current study, we determined that treating interleukin-1 beta (IL-1ß-stimulated chondrocyte cells) with cardamonin significantly reduced the release of nitric oxide (NO) and prostaglandin E2 (PGE2) and significantly inhibited the expression of pro-inflammatory proteins, including inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2). Cardamonin was also shown to: (1) inhibit the activation and production of matrix metalloproteinases (MMPs), (2) suppress the nuclear factor-κB (NF-κB) signaling pathway, (3) suppress the expression of toll-like receptor proteins, (4) activate the Nrf2 signaling pathway, and (5) increase the levels of antioxidant proteins heme oxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductase 1 (NQO1). The increase in antioxidant proteins led to corresponding antioxidant effects (which were abolished by Nrf2 siRNA). Our findings identify cardamonin as a candidate Nrf2 activator for the treatment and prevention of OA related to inflammation and oxidative stress.

Large-Pore Platelet-Rich Fibrin with a Mg Ring to Allow MC3T3-E1 Preosteoblast Migration and to Improve Osteogenic Ability for Bone Defect Repair.

Platelet-rich fibrin (PRF) is a natural fibrin meshwork material with multiple functions that are suitable for tissue engineering applications. PRF provides a suitable scaffold for critical-size bone defect treatment due to its platelet cytokines and rich growth factors. However, the structure of PRF not only promotes cell attachment but also, due to its density, provides a pool for cell migration into the PRF to facilitate regeneration. In our study, we used repeated freeze drying to enlarge the pores of PRF to engineer large-pore PRF (LPPRF), a type of PRF that has expanded pores for cell migration. Moreover, a biodegradable Mg ring was used to provide stability to bone defects and the release of Mg ions during degradation may enhance osteoconduction and osteoinduction. Our results revealed that cell migration was more extensive when LPPRF was used rather than when PRF was used and that LPPRF retained the growth factors present in PRF. Moreover, the Mg ions released from the Mg ring during degradation significantly enhanced the calcium deposition of MC3T3-E1 preosteoblasts. In the present study, a bone substitute comprising LPPRF combined with a Mg ring was demonstrated to have much potential for critical-size bone defect repair.

Biomechanical comparison of four tibial fixation techniques for meniscal root sutures in posterior medial meniscus root repair: A porcine study.

OBJECTIVE: This study hypothesized that the suture anchor of tibial fixation method of PMMR repair technique is the main factor which reduce the gap formation or over displacement of tear site in initial healing, and then investigated the fixation stability of 4 different tibial fixations through cyclic and ultimate failure load testing of meniscal root sutures. METHODS: Twenty-four porcine tibiae with intact medial meniscus roots were randomly assigned into 4 groups: transosseous suture, washer, suture anchor, or screw with washer. Each sample underwent cyclic loading followed by a load-to-failure test. Displacement, maximum load to failure, stiffness, and elongation at failure load were recorded. RESULTS: The maximum average load and displacement at failure for each of the repair groups were as follows: transosseous suture, 232.8 N and 12.16 mm; washer, 189.9 N and 21.5 mm; suture anchor, 140.6 N and 13.8 mm; and screw with washer, 167.9 N and 18.9 mm. The maximum stiffness values for each of the repair groups were as follows: transosseous suture, 19.5 ± 0.7 N/mm; washer, 21.5 ± 1.4 N/mm; suture anchor, 13.8 ± 0.7 N/mm; and screw with washer, 18.9 ± 3.9 N/mm. The mean elongation across the repairs for each of the repair groups after 1000 loading cycles was: transosseous suture, 3.74 ± 0.28 mm; washer, 3.04 ± 0.13 mm; suture anchor, 2.25 ± 0.33 mm; and screw with washer, 2.43 ± 0.19 mm. The mean elongation was significantly less with the suture anchor than with the other techniques (p < .05). CONCLUSION: Under physiological loading, our results indicate that a slower rehabilitation program with limited flexion and only partial weight bearing is advised when using a suture anchor because of the lower maximum load and stiffness. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: Tibial fixation using a washer or a screw with a washer is an effective and cost-saving technique when an option is required with high stiffness and low displacement at failure.

Pseudoaneurysm following hamstring tendon harvest in arthroscopic anterior cruciate ligament reconstruction: a case report.

BACKGROUND: Vascular injury is a very rare complication following arthroscopic knee surgery. This is the first report of pseudoaneurysm at the saphenous branch of the descending genicular artery complicating semitendinosus tendon harvest in arthroscopic anterior cruciate ligament reconstruction. CASE PRESENTATION: A 19-year-old male had developed large ecchymosis, focal swelling and tenderness around his posteromedial knee after an arthroscopic anterior cruciate ligament reconstruction. Compartment syndrome of the lower leg and deep vein thrombosis were ruled out. A pseudoaneurysm formation was confirmed through an angiography and coil embolization was performed. At one year follow up, the patient reported improved functional outcome with good stability of the knee. However, mild paresthesia over the posteromedial calf was noted due to the compression injury of the saphenous nerve by the hematoma. CONCLUSIONS: The pseudoaneurysm was presumed to result from accidental vascular injury while dissecting the accessory bands of the semitendinosus and was successfully treated by coil embolization. Care must be taken to section the expansions of the hamstring tendon, especially when the patient presents with underlying coagulopathy or vascular disease.

Astaxanthin attenuates joint inflammation induced by monosodium urate crystals.

Gouty arthritis is the one of the most painful arthritis and is caused by an inflammatory reaction. This study investigated whether astaxanthin (AXT), which has documented anti-inflammatory and antioxidant properties, exhibits protective effects against monosodium urate (MSU) crystal-induced inflammation. Cell viability of J774A.1 murine macrophages was assessed by AXT dose-dependent incubation by MTT assays, and expression levels of iNOS and COX-2 proteins as well as secretion of IL-1ß were also analyzed under MSU crystals stimulation with or without AXT treatment. The production of inflammatory mediators was found to significantly decrease with AXT treatment, and the formation of the inflammasome complex was also attenuated when cells were co-stimulated with MSU crystals and AXT. Furthermore, we found that expression of the MAPK pathway was downregulated in J774A.1 cells. AXT also inhibited the induction of COX-2 and IL-6 in human chondrocytes and synovial fibroblasts by western blots. Finally, an MSU crystal intra-articular injection rat model for gouty arthritis was utilized in which treatment groups received 5-daily intraperitoneal injections of AXT prior to MSU crystal stimulation, or once intra-articular injections of AXT following MSU crystal stimulation for 6 hours. Results of synovitis score analysis revealed that inflammation was significantly attenuated in the group which received intraperitoneal AXT injection prior to MSU crystal stimulation compared to the group which received MSU only. These results indicate that AXT attenuates the effects of MSU crystal-induced inflammation by suppressing the production of pro-inflammatory cytokines and inflammatory mediators. Our findings that the anti-inflammatory activities of AXT may be beneficial in the treatment of MSU crystal-induced arthritis.

Human Adipose-Derived Mesenchymal Stem Cells-Incorporated Silk Fibroin as a Potential Bio-Scaffold in Guiding Bone Regeneration.

Recently, stem cell-based bone tissue engineering (BTE) has been recognized as a preferable and clinically significant strategy for bone repair. In this study, a pure 3D silk fibroin (SF) scaffold was fabricated as a BTE material using a lyophilization method. We aimed to investigate the efficacy of the SF scaffold with and without seeded human adipose-derived mesenchymal stem cells (hASCs) in facilitating bone regeneration. The effectiveness of the SF-hASCs scaffold was evaluated based on physical characterization, biocompatibility, osteogenic differentiation in vitro, and bone regeneration in critical rat calvarial defects in vivo. The SF scaffold demonstrated superior biocompatibility and significantly promoted osteogenic differentiation of hASCs in vitro. At six and twelve weeks postimplantation, micro-CT showed no statistical difference in new bone formation amongst all groups. However, histological staining results revealed that the SF-hASCs scaffold exhibited a better bone extracellular matrix deposition in the defect regions compared to other groups. Immunohistochemical staining confirmed this result; expression of osteoblast-related genes (BMP-2, COL1a1, and OCN) with the SF-hASCs scaffold treatment was remarkably positive, indicating their ability to achieve effective bone remodeling. Thus, these findings demonstrate that SF can serve as a potential carrier for stem cells, to be used as an osteoconductive bioscaffold for BTE applications.

The high prevalence of sarcopenia and its associated outcomes following hip surgery in Taiwanese geriatric patients with a hip fracture.

BACKGROUND: Sarcopenia, which is a common risk factor for falls and fractures, affects the functional outcome and mortality in geriatric populations. However, the prevalence of sarcopenia among geriatric Taiwanese patients with a hip fracture is unknown, nor is the effect of sarcopenia on the outcome of hip surgery. METHODS: From December 2017 to February 2019, geriatric patients who underwent surgery for a hip fracture were prospectively enrolled. Basic demographic data, responses to questionnaires for dementia screening and quality of life (QoL) and daily living activities (ADL) before the injury were analyzed to identify any association with sarcopenia. The QoL and ADL were monitored at six months after the operation to determine the difference between hip fracture patients with or without sarcopenia. RESULTS: Of 139 hip fracture patients, 70 (50.36%) were diagnosed with sarcopenia. Accounting for all confounding factors in the multivariate logistic regression, lower body mass index (BMI), male gender and a weaker handgrip are the risk factors that are most strongly associated with a diagnosis of sarcopenia in geriatric patients with a hip fracture. Hip fracture patients with sarcopenia also have poor ADL and a lower QoL than patients without sarcopenia before the injury and six months after the operation. CONCLUSION: A high prevalence of sarcopenia among geriatric hip fracture patients is associated with a poor mid-term outcome following hip surgery. Clinicians must recognize the risk of sarcopenia, especially for male hip fracture patients with a lower BMI and a weaker handgrip.

The COX-2 inhibitor etoricoxib reduces experimental osteoarthritis and nociception in rats: The roles of TGF-ß1 and NGF expressions in chondrocytes.

BACKGROUND: Osteoarthritis (OA) is the most common joint disease, especially affecting the knee joint. Etoricoxib, a highly selective cyclooxygenase (COX)-2 inhibitor which can reduce postoperative pain after orthopaedic surgery. The aim of this study was to investigate the effects of oral etoricoxib on the development of OA and to examine concomitant changes in the nociceptive behaviour of rats. METHOD: OA was induced in wistar rats by anterior cruciate ligament transection (ACLT) of the right knee. The ACLT + etoricoxib groups received 6.7 or 33.3 mg/kg of oral etoricoxib three times a week for 12 consecutive weeks, starting at week 8 after ACLT. Nociceptive behaviours and changes in knee joint width during OA development were analyzed. Histopathological studies were then performed on the cartilage. Immunohistochemical analysis was performed to examine the effect of etoricoxib on the expression of transforming growth factor-beta (TGF-ß) and nerve growth factor (NGF) in articular cartilage chondrocytes. RESULTS: OA rats receiving etoricoxib showed a significantly lower degree of cartilage degeneration than the rats receiving placebo. Nociceptive behaviour studies showed significant improvement in the ACLT + etoricoxib groups compared to that in the ACLT group. Moreover, etoricoxib attenuated NGF expression, but increased TGF-ß expression, in OA-affected cartilage. CONCLUSIONS: Oral etoricoxib in a rat OA model (a) attenuates the development of OA, (b) concomitantly reduces nociception, and (c) modulates chondrocyte metabolism, possibly by inhibiting NGF expression and increasing TGF-ß expression. SIGNIFICANCE: Oral administration of etoricoxib can attenuate the development of OA, with an associated attenuation of nociceptive behaviour in an experimental rat OA model. Moreover, etoricoxib attenuated NGF expression, but enhanced TGF-ß expression in OA-affected chondrocytes. These findings may pave the way for further investigations of etoricoxib as a potential therapeutic target for the treatment of the inflammatory component in OA.

Fat distribution may predict intra- or extra-capsular hip fracture in geriatric patients after falling.

INTRODUCTION: Hip fractures can be divided into intra-capsular and extra-capsular fracture based on fracture location; these two types of fracture have different pathogeneses, treatments and prognoses. Many factors influence the patterns of hip fractures, including the injury mechanism, areal bone mineral density and the geometry of the hip. However, the relationship between body composition and hip fracture pattern has not yet been discussed. In this investigation, an analysis of the body compositions of geriatric patients with hip fractures were conducted to identify differences between fat and muscle distributions between patients with intra- and extra-capsular hip fractures. MATERIAL AND METHODS: From December 2017 to February 2019, 139 patients with a hip fracture were prospectively enrolled in this study. The groups of patients that were diagnosed as having intra- and extra-capsular hip fractures were compared in terms of patient demographics, pre-operative laboratory data, bone mineral density (BMD) and body composition including muscle and fat distributions obtained using dual-energy X-ray absorptiometry (DXA) . RESULTS: Eighty-six and 53 patients were diagnosed with intra-capsular and extra-capsular hip fractures, respectively. A significantly higher serum glucose level, a lower hemoglobin level, a lower T-score level in the proximal femur region, a lower T-score of all parts of interest, and a lower percentage fat content on the region of bilateral proximal hips (gynoid region) and in the lower limb region, were observed in patients with an extra-capsular hip fracture than in those with an intra-capsular hip fracture. However, with all confounding factors controlled for, only the T-score at the proximal femur, percentage fat content in the region of bilateral proximal hips and the ratio of android fat content to gynoid fat content (A/G ratio) are the most relevant factors in predicting the patterns of hip fracture in geriatric patients after falling. CONCLUSION: This work demonstrates that lower fat content in the region of bilateral proximal hips and a lower BMD on the proximal femur may predict greater vulnerability of geriatric patients to extra-capsular rather than intra-capsular hip fracture after a falling accident.

Chondroprotective Effects of Genistein against Osteoarthritis Induced Joint Inflammation.

Genistein is an isoflavone extracted from soybean (Glycine max). This compound has anti-inflammatory, anti-oxidative, and anti-cancer effects; however, the mechanism underlying the effects of genistein on IL-1ß-stimulated human osteoarthritis (OA) chondrocytes remains unknown. Our objectives in this study were to explore the anti-inflammatory effects of genistein on IL-1ß-stimulated human OA chondrocytes and to investigate the potential mechanisms which underlie them. Our results from an in-vitro model of osteoarthritis indicate that genistein inhibits the IL-1ß-induced expression of the catabolic factors nitric oxide synthase 2 (NOS2), cyclooxygenase 2 (COX-2), and matrix metalloproteinases (MMPs). Genistein was shown to stimulate Ho-1 expression, which has been associated with Nrf-2 pathway activation in human chondrocytes. In a rat model, genistein was also shown to attenuate the progression of traumatic osteoarthritis. Taken together, these results demonstrate the effectiveness of genistein in mediating the inflammation associated with joint disorders. Our results also indicate that genistein could potentially serve as an alternative therapeutic treatment for OA.

Intermittent Parathyroid Hormone Injection Can Decrease Femoral Head Collapse in the Vascular Deprivation of Rat Femoral Head Model.

BACKGROUNDS: Intermittent parathyroid hormone (intermittent PTH) injection has been shown to improve osteogenesis. We hypothesized that intermittent PTH injection could stimulate osteogenesis during the early phase of vascular deprivation-induced femoral neck osteonecrosis in a rat model. MATERIALS AND METHODS: Eighteen Sprague-Dawley rats were divided into three groups (normal saline [CON], PTH 10 µg/kg [PTH-H], and PTH 1 µg/kg [PTH-L]) for 8 weeks by subcutaneous injection. All rats were sacrificed at postoperative 8 weeks, and all underwent a micro-computed tomography (µ-CT) examination for bone quality and quantity evaluation and histomorphometric analysis for microscopic histologic differences. RESULTS: Under µ-CT examination, both the PTH-H and PTH-L groups revealed less bone resorption than the control group. The PTH-H group had a better bone protective effect than the PTH-L group. Bone mineral density was increased in the PTH-H and PTH-L groups compared to the control group. The uninjured left femoral head was enlarged in both PTH groups. The histologic examination showed that both PTH groups had new bone and cartilage formation. The control group had only dead bone without any osteogenesis. CONCLUSION: Intermittent PTH injection could decrease bone resorption and improve bone density, compared to the control group, in vascular deprivation of the femoral head in a rat model. High-level intermittent PTH injection had a better effect than low-level intermittent PTH injection.

A Modified Broström Repair with Transosseous Fixation for Chronic Ankle Instability: A Midterm Followup Study in Soldiers.

BACKGROUND: Various surgical techniques are available to reduce chronic instability of the lateral ankle ligament complex. The most effective method for these procedures remains controversial. This report presents a surgical technique that is similar to the Broström procedure and uses a modified, nonaugmented repair technique. MATERIALS AND METHODS: 38 soldiers with a history of chronic lateral ankle instability and poor ankle function underwent plication of the anterior talofibular ligament-lateral capsule complex with transosseous fixation of the calcaneofibular ligament through a fibular bone tunnel between 2004 and 2007. This study included 33 men and 5 women with a mean age of 25.6 years (range 18-36 years) at the time of surgery. Each patient was confirmed to have a history of chronic lateral ankle instability after an inversion injury, and symptoms had been noted for at least 1 year. The patients were followed up with stress radiographs, American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot functional score, and the Sefton assessment system. The mean followup period was 77.6 months (range 66-89 months). RESULTS: At the last evaluation, the talar tilt reduced from an average of 13.9° ± 2.4° before surgery to 3.8° ± 1.8° after surgery, and anterior drawer displacement reduced from 9.6 ± 2.9 mm to 2.3 ± 1.6 mm. The mean AOFAS ankle-hindfoot scale score for functional stability increased from 71.6 ± 4.0 points preoperatively to 95.6 ± 4.0 points postoperatively. As evaluated by the Sefton assessment system, 36 patients (95%) reported an excellent or good functional outcome. All patients resumed normal daily activities and active military duty after the surgery. CONCLUSION: The procedure described here could be considered a viable alternative option to anatomic reconstruction such as the modified Broström procedure and might be appropriate for the general population.

Novel technique for repairing posterior medial meniscus root tears using porcine knees and biomechanical study.

Transtibial pullout suture (TPS) repair of posterior medial meniscus root (PMMR) tears was shown to achieve good clinical outcomes. The purpose of this study was to compare biomechanically, a novel technique designed to repair PMMR tears using tendon graft (TG) and conventional TPS repair. Twelve porcine tibiae (n = 6 each) TG group: flexor digitorum profundus tendon was passed through an incision in the root area, created 5 mm postero-medially along the edge of the attachment area. TPS group: a modified Mason-Allen suture was created using no. 2 FiberWire. The tendon grafts and sutures were threaded through the bone tunnel and then fixed to the anterolateral cortex of the tibia. The two groups underwent cyclic loading followed by a load-to-failure test. Displacements of the constructs after 100, 500, and 1000 loading cycles, and the maximum load, stiffness, and elongation at failure were recorded. The TG technique had significantly lower elongation and higher stiffness compared with the TPS. The maximum load of the TG group was significantly lower than that of the TPS group. Failure modes for all specimens were caused by the suture or graft cutting through the meniscus. Lesser elongation and higher stiffness of the constructs in TG technique over those in the standard TPS technique might be beneficial for postoperative biological healing between the meniscus and tibial plateau. However, a slower rehabilitation program might be necessary due to its relatively lower maximum failure load.