Anti-inflammatory and anti-osteoarthritis effects of Cm-02 and Ck-02.

Osteoarthritis (OA) is a common degenerative joint disease characterized by progressive deterioration of articular cartilage. There have been reports that small molecule inhibitors have anti-osteoarthritis effects; however, the effects of 3-(4-chloro-2-fluorophenyl)-6-(2,4-difluorophenyl)-2H-benzo[e] [1,3]oxazine-2,4(3H)-dione (Cm-02) and 6-(2,4-difluorophenyl)-3-(3,4-difluorophenyl)-2H-benzo[e] [1,3]oxazine-2,4(3H)-dione (Ck-02), small molecule inhibitors which share many structural similarities with quercetin (a potent anti-inflammatory flavonoid), remain unclear. In this study, TNF-α-stimulated porcine and human chondrocyte models were used to investigate the inhibitory effects of Cm-02 and Ck-02 on the molecular mechanisms underlying the anti-OA effects. TNF-α was used to stimulate porcine and human chondrocytes to mimic immunomodulatory potency in-vitro. Anti-osteoarthritic effects were characterized in terms of protein and mRNA levels associated with the pathogenesis of OA. We also examined (1) the inducible nitric oxide synthase (iNOS)-nitric oxide (NO) system in cultured chondrocytes, (2) matrix metalloproteinases (MMPs) in cultured chondrocytes, and (3) aggrecan degradation in cartilage explants. Finally, we tested the activation of nuclear factor-kappaB (NF-κB), interferon regulatory factor-1 (IRF-1), and activate the protein-1 (AP-1), and we tested the signal transduction and activation of transcription-3 (STAT-3). Our results indicate that, in chondrocytes, Cm-02 and Ck-02 inhibit TNF-α induced NO production, iNOS, MMP, the expression of disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS), and the enzyme activity of MMP-13. Furthermore, both Cm-02 and Ck-02 were found to stimulate TNF-α, which has been shown to suppress the activation of several transcription factors, including NF-κB, STAT-3, and IRF-1 in porcine and human chondrocytes. Cm-02 and Ck-02 were also found to help prevent the release of proteoglycans from cartilage explants. Our findings demonstrate that both Cm-02 and Ck-02 have potent anti-inflammatory activities and the ability to protect cartilage in an OA cell model. These findings indicate that Cm-02 and Ck-02 have the potential to be further developed for the therapeutic treatment of OA.

No difference in the functional improvements between unilateral and bilateral total knee replacements.

BACKGROUND: Differences between staged bilateral total knee replacement (TKR) and simultaneous bilateral TKR have been investigated, but few studies have investigated differences in the functional improvements resulting from these methods. Therefore, this study investigates the different functional improvements between staged bilateral total knee TKR and simultaneous bilateral TKR. METHODS: Among 144 potential bilateral TKR patients who were included in this study, 93 (64.6%) patients selected unilateral TKR and 51 (35.4%) selected bilateral TKR. Functional improvements were assessed using the Western Ontario and McMaster University osteoarthritis index (WOMAC) and the Medical Outcomes Trust Short Form-36 (SF-36), and patients were interviewed pre-operatively and after 6 months. A generalized equation was used to test for differences in functional improvements. RESULTS: After TKR, pain, stiffness, function and total WOMAC scores were significantly reduced in both groups, with mean changes from - 26.6 to - 41.4 and from - 27.5 to - 42.2.The mean health change of SF-36 scores, physical component and mental component scores changed to 45.2 ± 18.2, 74.0 ± 15.4 and 77.0 ± 9.6, respectively, in Group 1 and 47.1 ± 17.1, 74.0 ± 15.2 and 75.5 ± 12.1, respectively, in Group 2. Unilateral and simultaneous bilateral TKR produce similar functional improvements, although current work status may be a novel impact factor. CONCLUSION: No differences in functional improvements were identified between patients who selected unilateral versus bilateral TKR, indicating no recommendation for one procedure over the other.

Chondroprotective Effects and Mechanisms of Dextromethorphan: Repurposing Antitussive Medication for Osteoarthritis Treatment.

Osteoarthritis (OA) is the most common joint disorder and primarily affects older people. The ideal anti-OA drug should have a modest anti-inflammatory effect and only limited or no toxicity for long-term use. Because the antitussive medication dextromethorphan (DXM) is protective in atherosclerosis and neurological diseases, two common disorders in aged people, we examined whether DXM can be protective in pro-inflammatory cytokine-stimulated chondrocytes and in a collagen-induced arthritis (CIA) animal model in this study. Chondrocytes were prepared from cartilage specimens taken from pigs or OA patients. Western blotting, quantitative PCR, and immunohistochemistry were adopted to measure the expression of collagen II (Col II) and matrix metalloproteinases (MMP). DXM significantly restored tumor necrosis factor-alpha (TNF-α)-mediated reduction of collagen II and decreased TNF-α-induced MMP-13 production. To inhibit the synthesis of MMP-13, DXM blocked TNF-α downstream signaling, including I kappa B kinase (IKK)α/ß-IκBα-nuclear factor-kappaB (NF-κB) and c-Jun N-terminal kinase (JNK)-activator protein-1 (AP-1) activation. Besides this, DXM protected the CIA mice from severe inflammation and cartilage destruction. DXM seemed to protect cartilage from inflammation-mediated matrix degradation, which is an irreversible status in the disease progression of osteoarthritis. The results suggested that testing DXM as an osteoarthritis therapeutic should be a focus in further research.

Arthroprotective Effects of Cf-02 Sharing Structural Similarity with Quercetin.

In this study, we synthesized hundreds of analogues based on the structure of small-molecule inhibitors (SMIs) that were previously identified in our laboratory with the aim of identifying potent yet safe compounds for arthritis therapeutics. One of the analogues was shown to share structural similarity with quercetin, a potent anti-inflammatory flavonoid present in many different fruits and vegetables. We investigated the immunomodulatory effects of this compound, namely 6-(2,4-difluorophenyl)-3-(3-(trifluoromethyl)phenyl)-2H-benzo[e][1,3]oxazine-2,4(3H)-dione (Cf-02), in a side-by-side comparison with quercetin. Chondrocytes were isolated from pig joints or the joints of patients with osteoarthritis that had undergone total knee replacement surgery. Several measures were used to assess the immunomodulatory potency of these compounds in tumor necrosis factor (TNF-α)-stimulated chondrocytes. Characterization included the protein and mRNA levels of molecules associated with arthritis pathogenesis as well as the inducible nitric oxide synthase (iNOS)⁻nitric oxide (NO) system and matrix metalloproteinases (MMPs) in cultured chondrocytes and proteoglycan, and aggrecan degradation in cartilage explants. We also examined the activation of several important transcription factors, including nuclear factor-kappaB (NF-κB), interferon regulatory factor-1 (IRF-1), signal transducer and activator of transcription-3 (STAT-3), and activator protein-1 (AP-1). Our overall results indicate that the immunomodulatory potency of Cf-02 is fifty-fold more efficient than that of quercetin without any indication of cytotoxicity. When tested in vivo using the induced edema method, Cf-02 was shown to suppress inflammation and cartilage damage. The proposed method shows considerable promise for the identification of candidate disease-modifying immunomodulatory drugs and leads compounds for arthritis therapeutics.

Infusion of Porcine-Derived Amniotic Fluid Stem Cells for Treatment of Experimental Colitis in Mice.

Recently, stem cells have offered an alternative treatment for inflammatory bowel disease (IBD) or colitis to overcome the poor outcomes associated with current therapies. Amniotic fluid-derived stem cells (AFSCs) have the potential for the regeneration of impaired organs and the recovery of normal physiologic functions of damaged tissues without ethical concerns or risk of tumor formation. In this work, we aimed to examine the therapeutic effects of infusion of porcine AFSCs (pAFSCs) in dextran sulfate sodium (DSS)-induced colitis in mice. Treatment with pAFSCs was shown to inhibit the shortening of the colon after induction of colitis and dramatically ameliorated the body weightloss induced by the DSS treatment. In addition, pAFSCs could also reduce the extent of the inflamed area represented by epithelial mesenchymal transformation in the colitis mice. The levels of the inflammatory cytokines interleukin 6 (IL-6) and interferon gamma (IFN-γ) were also reduced in colitis mice transplanted with pAFSCs. In conclusion, pAFSCs can ameliorate experimental colitis in mice, suggesting that they may be a potential treatment for IBD or colitis.

Combined Innovative Portal Arthroscopy and Fluoroscopy-Assisted Reduction and Fixation in Subtle Injury of the Lisfranc Joint Complex: Analysis of 10 Cases.

Subtle injuries of the Lisfranc joint complex are uncommon and difficult to diagnose clinically and thus are easily missed even by experienced orthopedic doctors. Misdiagnosed injuries can lead to chronic disability until eventual fusion surgery. We describe 10 cases diagnosed with subtle injury of the Lisfranc joint that were treated with combined innovative portal arthroscopy and fluoroscopy-assisted reduction and percutaneous screw fixation in an interfragmentary fashion. The distance between the first and second metatarsals (the Lisfranc distance) and that between the medial cuneiform and fifth metatarsal base (foot arch height) was measured before and after surgery. The American Orthopaedic Foot and Ankle Society function score was evaluated perioperatively. The average preoperative and postoperative Lisfranc distance was 4.38 ± 0.39 mm and 2.68 ± 0.9 mm, the foot arch height was 12.63 ± 2.75 mm and 21.80 ± 3.50 mm, and the American Orthopaedic Foot and Ankle Society score was 59.1 ± 5.69 and 86.8 ± 10.1, respectively. Of the 10 patients, 3 had excellent outcomes, 6 had good outcomes, and 1 had a fair outcome. In conclusion, we report a useful and minimally invasive surgery for acute, subacute, and even chronic subtle injury of the Lisfranc joint. The Lisfranc distance, foot arch height, and function of the foot were restored clinically, and all measurements showed statistically significant differences.

Effects of Collagen Crosslink Augmentation on Mechanism of Compressive Load Sharing in Intervertebral Discs.

Exogenous crosslinking has been shown to have potential for treating disc degeneration and back pain due to its ability to increase the strength and toughness of the annulus fibrosus, increase intervertebral joint stability, decrease intradiscal pressure, and increase fluid flow through the disc. Some results imply that crosslink augmentation may also lead to changes in the compressive load sharing properties of the disc. The objective of the present study was to evaluate directional stress distribution changes of the disc following genipin crosslinking treatment. Bovine lumbar motion segments were randomly divided into control and crosslinked groups. Annular strains were determined from simultaneous deformation measurements at various time points during compressive creep testing. Four stress components of the annulus were then calculated according to the previously measured modulus data. Immediately after the application of a 750-N compressive load, mean axial and radial compressive stresses in the crosslinked group were twofold higher than control means. Conversely, mean lamellae-aligned and circumferential tensile stresses of the crosslinked discs were 8- and threefold lower, respectively, compared to control means. After 1-h creep loading, the two compressive mean stresses in both the control and genipin-crosslinked specimens increased approximately threefold from their initial 750-N-loaded values. The two tensile mean stresses in the crosslinked group remained lower than the respective levels of the control means after creep loading. A greater proportion of annular compressive load support under compressive creep loading, with a commensurate decrease in both tensile stresses and strains, was seen in the discs following exogenous crosslink augmentation.

Bilateral passive leg raising attenuates and delays tourniquet deflation-induced hypotension and tachycardia under spinal anaesthesia: a randomised controlled trial.

BACKGROUND: The pneumatic tourniquet is frequently used in total knee arthroplasty. Tourniquet deflation may result in hypotension and tachycardia caused by the rapid shift of blood volume back to the ischaemic limb and a decrease in cardiac preload. Passive leg raising (PLR) represents a 'self-volume challenge' that can result in an increase in preload. Such a PLR-induced increase in preload was hypothesised to attenuate the decrease in preload resulting from tourniquet deflation. OBJECTIVE: To evaluate the effect of PLR on hypotension and tachycardia following tourniquet deflation. DESIGN: A randomised controlled trial. SETTING: Single medical centre. PATIENTS: Seventy patients who underwent unilateral total knee arthroplasty were randomised into two groups: tourniquet deflation with PLR (n = 35) or without PLR (control group, n = 35). INTERVENTION(S): Patients in both groups were administered a single dose of plain bupivacaine for spinal anaesthesia. The pneumatic tourniquet was inflated on the thigh and the surgery was performed. The study composed of four steps: for the PLR group, step 1 - inflation of the tourniquet while the patient was supine; step 2 - the patient's legs were raised to a 45° angle; step 3 - the tourniquet was deflated while the patient's legs were still raised; and step 4 - the legs were returned to the supine position. In the control group, the same perioperative procedure was used, but PLR was not conducted. MAIN OUTCOME MEASURES: The patients' blood pressure and heart rate were measured before, during and after tourniquet deflation. RESULTS: After tourniquet deflation, the magnitude of the changes in blood pressure and heart rate was less in the PLR group than that in the control group. In addition, the blood pressure nadir also occurred later in the PLR group than in the controls. CONCLUSION: Bilateral PLR is a simple, reversible manoeuvre that mimics rapid fluid loading. Bilateral PLR attenuates the severity of, and delays the time to, hypotension and tachycardia following deflation of a lower limb tourniquet. TRIAL REGISTRATION: ClinicalTrials.gov number NCT01592669.

Arthroscopic excision of ganglion cysts of the posterior cruciate ligaments using posterior trans-septal portal.

PURPOSE: To evaluate clinical outcomes of arthroscopic excision of ganglion cysts involving the posterior cruciate ligament (PCL) using the posterior trans-septal portal in the knee. METHODS: A retrospective study was performed of 15 cases of ganglion cyst involving the PCL treated at our institution over a period of 4 years. All the cysts were diagnosed and had their location confirmed preoperatively by magnetic resonance imaging (MRI). All the cysts were excised arthroscopically through the posterior trans-septal portal. All patients were followed up with MRI evaluation at a mean of 36 months after surgery. In addition, International Knee Documentation Committee (IKDC) scores and range of motion (ROM) were obtained preoperatively and postoperatively simultaneously with MRI to assess the surgical outcomes. RESULTS: Most of the patients were male patients, and the mean age was 32 years. The most common presenting complaint was pain and difficulty in knee flexion. Preoperatively, the mean ROM was 3° to 110° and the mean IKDC score was 53 (range, 38 to 67; SD, 7.9). The location of the main cystic component was posterior to the PCL in 14 patients (93%) and anterior to the PCL in 1 patient (7%). After surgery, MRI evaluation at a mean follow-up time of 36 months showed no cyst recurrence. Postoperatively, the mean IKDC score was 91 (range, 70 to 99; SD, 9.3) and the mean ROM was 3° to 128°. CONCLUSIONS: Ganglion cysts associated with the PCL can cause knee pain and limitation of knee flexion. MRI evaluation is a noninvasive method of diagnosing PCL ganglion cysts. Arthroscopic excision through the posterior trans-septal portal is a good option for relieving pain and preventing cyst recurrence. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

Treatment of septic knee arthritis: comparison of arthroscopic debridement alone or combined with continuous closed irrigation-suction system.

BACKGROUND: Arthroscopic debridement has been widely adapted as initial treatment for septic knee arthritis. Although isolated cases of arthroscopic debridement combined with irrigation-suction systems have been reported, a comparison of two techniques has not been performed, to our knowledge. The purpose of this study was to compare the two methods of treatment. METHODS: From January 1996 to December 2008, 39 patients with 39 septic knee arthritis treated in our institution were retrospectively analyzed. Nineteen knees were initially treated with arthroscopic debridement alone (group I), and 20 knees were initially treated with arthroscopic debridement combined with continuous closed irrigation-suction system (group II). The clinical presentation, laboratory and microbiologic findings, hospital course, and clinical outcomes were compared between the two groups. RESULTS: The mean delay between the onset of the symptoms and treatment had a significant effect on the clinical outcomes. When the comparison included all the patients in the series, no significant difference between the two groups was found with regard to the number of operation procedures required or the length of the hospital stay. However, when the comparison was separated from the initial stage of infection, it was found that in stage II infection, patients had fewer reoperations and in stages II and III infection, a shorter hospital stay in group II than in group I (p < 0.05). There was no significant difference in the functional results between the two groups. CONCLUSIONS: The early diagnosis and aggressive initiation of treatment carried the success of therapy in septic knee arthritis. Arthroscopic debridement combined with continuous closed irrigation-suction system is an effective treatment for patients with septic knee arthritis; these patients had fewer operations and a shorter hospital stay than did patients who had received arthroscopic debridement alone.

Fallopian tube stem cell medium of porcine and bovine: In vitro regenerative effect on maturation and parthenogenesis of porcine oocytes.

Assisted reproductive technology (ART) has been widely developed over the decades. This advanced technology has shown efficacy in the conception and breeding of an animal. However, several issues such as polyspermy, low maturation rate, and low development rate in vitro remain unresolved. Fallopian tube derived cells are proposed to promote the maturation and development of oocyte. This study aims to characterize porcine (PFTSC) and bovine fallopian tube stem cell (BFTSC) while comparing allogeneic and xenogeneic paracrine effects on porcine oocyte. FTSC of Taiwan yellow cattle (B. indicus) and porcine (Landrace x Yorkshire dam x Duroc) were isolated and identified. Conditioned media (Medium 199 or PZM-3) from porcine and bovine was collected and added to porcine cells during in vitro maturation (IVM) and in vitro culture (IVC). Both PFTSC and BFTSC expressed little CD44, CD105, and CD4. Both cells were induced to transform into chondrocytes, very few cells gave rise to osteocytes and adipocytes. IVM test showed a significant elevation of maturation rate in both groups (Porcine: 66.5 ± 3.5% > 55.9 ± 1.7%, p < .05; Bovine: 68.9 ± 2.3% > 55.9 ± 1.7%, p < .05). IVC test demonstrated markedly reduction of blastocyst in both groups. In a diluted conditioned medium with different concentration, 25% and 50% PFTSC showed a decrease in blastocyst rate which is significantly different, but BFTSC demonstrated no significant difference. PFTSC and BFTSC possessed properties of stem cells. Conditioned media from both PFTSC and BFTSC could improve maturation rate but not blastocyst rate in vitro.

Prevalence of flexible flatfoot in Taiwanese school-aged children in relation to obesity, gender, and age.

The objective of this study was to determine the prevalence of flexible flatfoot in elementary school children in Taiwan and evaluate the relationship between flatfoot and obesity, gender, and age. A sample of 2,083 children, between 7 and 12 years of age from public elementary schools in northern Taiwan was analyzed. Children were stratified into groups according to age: 7, 8, 9, 10, 11, or 12 years old. Demographic information was obtained, and the presence of flatfoot determined by footprint analysis and grading according to Denis flatfoot staging. A total of 1,222 (59%) children were documented with flatfoot. The incidence percentages of flatfoot were: 67% of males, 49% of females, and 75%, 65%, 57%, and 48% of obese, overweight, normal weight, and underweight children, respectively. A preponderance of flatfoot was observed among 8-year-olds. Multivariate analyses indicated that 8- and 9-year-olds were 1.52 and 0.72 times more likely to have flatfoot than 7-year-olds. Males were twice as likely to have flatfoot as females. Children who were obese or overweight were 2.66 and 1.39 times more likely to have flatfoot than those of average weight. The results of this study indicate that the prevalence of flexible flatfoot is highest among males who are obese and overweight, particularly in the age range of 7 to 8 years.

Anatomic reconstruction of neglected Achilles tendon rupture with autogenous peroneal longus tendon by EndoButton fixation.

BACKGROUND: Neglected or chronic rupture of the Achilles tendon usually needs a reconstruction procedure. Many graft sources have been reported for this procedure, such as a proximal V-Y gastrocnemius tendon flap, flexor hallucis longus tendon, fascia lata, plantaris tendon, synthetic materials, and peroneus brevis. However, how to fix the graft at the calcaneal site remains controversial. METHODS: An alternative technique to anatomically reconstruct the Achilles tendon using an autogenous peroneal longus tendon with EndoButton-CL fixation at the calcaneal site for treatment of a patient who had a chronic neglected rupture of the Achilles tendon is described. RESULTS: The patient was allowed to begin gentle exercise, such as swimming and cycling 12 weeks after surgery, and encouraged to augment rehabilitation of hindfoot eversion and ankle plantar flexion. The ankle plantar flexion and hindfoot eversion strength was not reduced after active rehabilitation in 2.5 years of follow-up. CONCLUSIONS: Our technique reuses two small central incisions, thus, preserving skin integrity as much as possible to reduce wound breakdown or infection. The management of chronic or neglected Achilles tendon rupture by autogenous peroneal longus tendon with EndoButton-CL fixation at the calcaneal site is an anatomic and safe, but technically demanding technique.

Comparison of different sizes of bioabsorbable interference screws for anterior cruciate ligament reconstruction using bioabsorbable bead augmentation in a porcine model.

PURPOSE: The aim of this study was to compare the initial fixation strength of tendon grafts between different sizes of bioabsorbable interference screws (BioScrew; Linvatec, Largo, FL) with bioabsorbable bead (EndoPearl; Linvatec) augmentation through biomechanical analysis of a porcine femoral bone model. METHODS: Forty pairs of porcine femurs and porcine flexor digitorum profundus tendons were divided into control and study groups. In the control group 8 x 30-mm BioScrews alone (n = 10) were inserted, whereas different sizes of BioScrews, measuring 7 x 30 mm (n = 10), 8 x 30 mm (n = 10), and 9 x 30 mm (n = 10), with 8-mm EndoPearl augmentation were inserted individually for fixation of tendon grafts in the study groups. All specimens were cyclically loaded with axial forces between 50 and 250 N at 1 Hz for 3,000 cycles and then incrementally loaded to failure at a rate of 150 mm/min. RESULTS: BioScrews with EndoPearl augmentation had a significantly higher failure load than BioScrews alone (8-mm BioScrew alone v 8-mm BioScrew and EndoPearl, P < .05). There were no significant differences in the ultimate failure load (8 mm v 7 mm and 9 mm, P = .201 and P = .871, respectively), stiffness (8 mm v 7 mm and 9 mm, P = .789 and P = .823, respectively), displacement (8 mm v 7 mm and 9 mm, P = .695 and P = .781, respectively), and bone mineral density (P = .728 for all comparisons) except insertion torque (8 mm v 7 mm and 9 mm, P = .045 and P = .518, respectively) between study groups. Less tendon laceration by the screw thread was noted in the group in which smaller-sized BioScrews were used. CONCLUSIONS: When EndoPearl augmentation was used, smaller-sized BioScrews (BioScrew size 1 mm smaller than bone tunnel) offered equivalent graft fixation strength to BioScrews of similar or larger sizes. CLINICAL RELEVANCE: Smaller-sized BioScrews can be chosen if EndoPearl augmentation has been used, and EndoPearl augmentation may reduce the risk of tendon rupture while BioScrews are inserted.

Outcomes of distal femoral fractures treated with minimally invasive plate osteosynthesis versus open reduction internal fixation with combined locking plate and interfragmentary screws.

PURPOSE: Fractures of the distal femur remain challenging to treat, and numerous fixation methods are designed to promote stability and fracture healing. Locking plate constructs have recently become the mainstream fixation method, but debate exists on whether to use locking plates alone or to augment them with interfragmentary screws. This article compares outcomes of distal femur fractures treated with a single locking plate alone versus those treated with a locking plate and interfragmentary screws. METHODS: We retrospectively reviewed 57 patients treated for distal femur fractures from 2010 to 2013. Patients were divided into two groups: Those treated with a locking plate alone utilizing the minimally invasive plate osteosynthesis (MIPO) technique and those treated with combination of a locking plate and interfragmentary screws using an open technique. Postoperative outcomes were obtained via a manual chart review. Fracture healing and callus indices were evaluated from radiographs. RESULTS: 9 patients required revision surgery in the locking plate alone group (6 for persistent nonunion and 3 for varus deformity). Only two patients in the combination group required revisions (both for nonunion). Average time to full weight bearing was 19.54 weeks in the locking plate group versus 14.57 weeks in the combination group (p = 0.004). At the time of full weight bearing, frontal (1.15 versus 1.11, p = 0.004) and sagittal (1.22 versus 1.15, P = 0.008) callus indices were both significantly greater in the locking plate group. CONCLUSIONS: In this study, the combination of a locking plate and interfragmentary screws achieved suitable stability and a faster time to full weight bearing than using a locking plate alone. Surgeons should consider combining a locking plate with interfragmentary screws as an effective method for fixation of distal femur fractures, particularly in cases when plate fixation alone fails to provide adequate fracture stability.

Increased COUP-TFII Expression Mediates the Differentiation Imbalance of Bone Marrow-Derived Mesenchymal Stem Cells in Femoral Head Osteonecrosis.

OBJECTIVE: Bone marrow-derived mesenchymal stem cells (BMSCs) have multilineage differentiation potential, which allows them to progress to osteogenesis, adipogenesis, and chondrogenesis. An imbalance of differentiation between osteogenesis and adipogenesis will result in pathologic conditions inside the bone. This type of imbalance is also one of the pathological findings in osteonecrosis of the femoral head (ONFH). Chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) was previously reported to mediate the differentiation of mesenchymal stem cells. This study investigated the expression of the osteogenesis regulator Runx2, osteocalcin, the adipogenesis regulator PPARγ, and COUP-TFII in the femoral head tissue harvested from ONFH patients, and characterized the effect of COUP-TFII on the differentiation of primary BMSCs. METHODS: Thirty patients with ONFH were recruited and separated into 3 groups: the trauma-, steroid- and alcohol-induced ONFH groups (10 patients each). Bone specimens were harvested from patients who underwent hip arthroplasty, and another 10 specimens were harvested from femoral neck fracture patients as the control group. Expression of the osteogenesis regulator Runx2, osteocalcin, the adipogenesis regulator PPARγ, C/EBP-α, and COUP-TFII was analyzed by Western blotting. Primary bone marrow mesenchymal cells were harvested from ONFH cells treated with COUP-TFII RNA interference to evaluate the effect of COUP-TFII on MSCs. RESULTS: ONFH patients had significantly increased expression of the adipogenesis regulator PPARγ and C/EBP-α and decreased expression of the osteogenesis regulator osteocalcin. ONFH bone tissue also revealed higher COUP-TFII expression. Immunohistochemical staining displayed strong COUP-TFII immunoreactivity adjacent to osteonecrotic trabecular bone. Increased COUP-TFII expression in the bone tissue correlated with increased PPARγ and decreased osteocalcin expression. Knockdown of COUP-TFII with siRNA in BMSCs reduced adipogenesis and increased osteogenesis in mesenchymal cells. CONCLUSION: Increased COUP-TFII expression mediates the imbalance of BMSC differentiation and progression to ONFH in patients. This study might reveal a new target in the treatment of ONFH.

The effect of endoscopic bursectomy with mini-open partial scapulectomy on snapping scapula syndrome.

BACKGROUND: The purpose of this study was to evaluate an alternate method using endoscopic bursectomy with mini-open partial scapulectomy for treating snapping scapula in patients who did not respond to conservative therapy. MATERIALS AND METHODS: Between November 2000 and November 2004, endoscopic bursectomy with mini-open partial scapulectomy was performed in 12 cases with snapping scapula. Four cases had bilateral involvement; eight had unilateral involvement. Nine cases had a history of trauma. The mean duration of conservative therapy was 4.1 (range, 1-8) y. The procedure was performed at the superomedial angle of the scapula in 10 cases, at the medial border in two cases, and at the inferomedial angle in one case. The mean postoperative follow-up was 3.1 (range, 2-5) years. RESULTS: The American Shoulder and Elbow Surgeon score increased (preoperatively, 36.3 to postoperatively, 88.3), the Simple Shoulder Test score increased (3.8 to 10.1), and the Visual Analogue Score decreased (8.3 to 2.3) significantly (all P < 0.01). The snapping sound and pain improved in 10 of 12 cases. All patients returned to work. CONCLUSION: Endoscopic bursectomy with mini-open partial scapulectomy is a reliable, alternate treatment for snapping scapula.

Retinoid acid inhibits IL-1-induced iNOS, COX-2 and chemokine production in human chondrocytes.

This study aims to investigate the effects and mechanisms of all-trans retinoic acid (t-RA) on interleukin(IL)-1-induced production of several inflammatory mediators in human chondrocytes. The cartilage from OA patients receiving total knee or total hip replacement was obtained and chondrocytes were prepared. Chemokine concentrations were measured by ELISA. The expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) was determined by Western blotting and/or RT/PCR. Nitrite levels were measured by Griess assays. The DNA-binding activity and transcriptional activity of activator protein-1 (AP-1) were measured by electrophoresis mobility shift assay and luciferase assay. We showed that t-RA suppressed IL-1-induced release of chemokines, including regulated upon activation, normal T cell expressed and secreted (RANTES), monocyte chemoattractant protein 2 (MCP-2), macrophage inflammatory protein-1alpha (MIP-1alpha) and MIP-1beta. Four different retinoid derivatives all preserved inhibitory effects albeit the potency was different. t-RA potently suppressed IL-1-induced expression of iNOS and COX-2 and production of nitric oxide and prostaglandin E(2). In consistent with the results in primary chondrocytes, t-RA down-regulated IL-1-induced AP-1 DNA binding activity and transcriptional activity in a human fibroblast-like (commercially labeled as chondrocyte) cell line. By examining the effect of a c-jun N-terminal kinase (JNK) specific inhibitor, we showed that the suppression of JNK-AP-1 signaling was enough to inhibit IL-1-induced production of chemokines and activation of iNOS and COX-2 pathways. Collectively, our results raise a therapeutic option that intra-articular administration of retinoid derivatives at 10-1000 nanomolar concentrations may be effective to suppress the progression of inflammatory OA.

Disassembly and dislocation of a bipolar hip prosthesis.

Dislocation of a hip prosthesis is a common complication. In usual cases of hip prosthesis dislocation, the prosthetic femoral head comes out from either the natural acetabular cavity in a bipolar hemiarthroplasty or the prosthetic acetabulum in a total hip arthroplasty. Only a few cases of bipolar hip prosthesis dislocation due to dissociation between the polyethylene and inner head of the prosthesis have been reported. We describe a rare case of disassembly of the inner head from the bipolar outer prosthesis in an osteoarthritic acetabulum. A 72-year-old woman had undergone bipolar hemiarthroplasty due to fracture of the left femoral neck about 10 years previously. Recently, she sustained an injury after falling from a chair, and examinations revealed an unusual disassembly-dislocation of the bipolar hip prosthesis. We classified this failure in our patient as a type II failure, representing extreme varus position of the outer head in the acetabulum, dislocation of the inner head from the outer head, and a detached locking ring around the stem neck. This mechanism of failure as shown in our patient rarely occurs in the bipolar prosthesis of the self-centering system. Osteoarthritic change of the acetabulum would place the outer head in the varus position, increasing wear on the beveled rim by impinging the femoral stem neck and causing dislodgment of the inner locking ring and consequent disassembly-dislocation of the inner head.

Long-term functional outcomes after repair of rotator cuff tears correlated with atrophy of the supraspinatus muscles on magnetic resonance images.

We determined the relationship between atrophy of the supraspinatus muscle and functional outcomes in 27 patients with full-thickness rotator cuff tears who underwent arthroscopic acromioplasty and mini-open cuff repair. Before surgery, all underwent a physical examination and magnetic resonance imaging of the involved shoulder. Using image-processing software, we measured the cross-sectional area of the total supraspinatus muscle (including regions of fatty degeneration and atrophy) and of the atrophic supraspinatus muscle on sagittal oblique images obtained about 20 mm proximal to the glenoid surface. The atrophic-to-total ratio (A/T ratio) of these areas was then calculated. We assessed functional outcomes by the Constant and Murley functional score at long-term follow-up. The correlation between the A/T ratios and the functional ratings was statistically analyzed. The results demonstrated a significant positive correlation between A/T ratios of the supraspinatus muscle and functional outcomes.