Introduction: The aim of this study was to evaluate, for the first time, the differences in gene expression profiles of normal and osteoarthritic (OA) subchondral bone in human subjects. Methods: Following histological assessment of the integrity of overlying cartilage and the severity of bone abnormality by micro-computed tomography, we isolated total RNA from regions of interest from human OA (n = 20) and non-OA (n = 5) knee lateral tibial (LT) and medial tibial (MT) plateaus. A whole-genome profiling study was performed on an Agilent microarray platform and analyzed using Agilent GeneSpring GX11.5. Confirmatory quantitative reverse-transcription polymerase chain reaction (qRT-PCR) analysis was performed on samples from 9 OA individuals to confirm differential expression of 85 genes identified by microarray. Ingenuity Pathway Analysis (IPA) was used to investigate canonical pathways and immunohistochemical staining was performed to validate protein expression levels in samples. Results: A total of 972 differentially expressed genes were identified (fold change ≥ ± 2, P ≤0.05) between LT (minimal degeneration) and MT (significant degeneration) regions from OA samples; these data implicated 279 canonical pathways in IPA. The qRT-PCR data strongly confirmed the accuracy of microarray results (R² = 0.58, P <0.0001). Novel pathways were identified in this study including Periostin (POSTN) and Leptin (LEP), which are implicated in bone remodeling by osteoblasts. Conclusions: To the best of our knowledge, this study represents the most comprehensive direct assessment to date of gene expression profiling in OA subchondral bone. This study provides insights that could contribute to the development of new biomarkers and therapeutic strategies for OA.

Background: The efficacy and tolerability of 500-730 kDa sodium hyaluronate (Hyalgan^®) for treatment of osteoarthritis (OA) pain has been established in clinical trials, but few data are available in the Asian population. We conducted a randomized, double-blind, multicenter, placebo-controlled study to evaluate the efficacy and tolerability of this preparation in a Taiwanese population. Methods: Two hundred patients with mild to moderate OA of the knee were randomized to receive five weekly intra-articular injections of sodium hyaluronate or placebo. The primary efficacy outcome was the change from baseline to Week 25 in patients' evaluation of pain using a 100-mm visual analog scale (VAS) during the 50-foot walking test. Additional outcomes included Western Ontario and McMaster Universities (WOMAC) scores, time on the 50-foot walking test, patient's and investigator's subjective assessment of effectiveness, acetaminophen consumption, and the amounts of synovial fluid. Results: The Hyalgan^® treatment group showed a significantly greater improvement from baseline to Week 25 in VAS pain on the 50-foot walking test than the placebo group (p = 0.0020). The Hyalgan^® group revealed significant improvements from baseline to week 25 in WOMAC pain and function score than the placebo group (p = 0.005 and 0.0038, respectively) Other outcomes, such as time on the 50-foot walking test and subjective assessment of effectiveness, did not show any significant difference between groups. Both groups were safe and well tolerated. Conclusions: The present study suggests that five weekly intra-articular injections of sodium hyaluronate are well tolerated, can provide sustained relief of pain, and can improve function in Asian patients with osteoarthritis of the knee. Level of Evidence: Therapeutic study, Level I-1a (randomized controlled trial with a significant difference). Trial registration: ClinicalTrials.gov Identifier: NCT01319461

Background: Severe glenoid bone loss in recurrent anterior glenohumeral instability is rare and difficult to treat. Purpose: The authors present a surgical technique using allogeneic bone grafting for open anatomic glenoid reconstruction in addition to the capsular shift procedure. Study Design: Case series; Level of evidence, 4. Methods: Nine consecutive patients with a history of recurrent anterior shoulder instability underwent reconstruction of large bony glenoid erosion with a femoral head allograft combined with an anteroinferior capsular shift procedure. Preoperative computed tomographic and arthroscopic evaluation was performed to confirm a ≥120° osseous defect of the anteroinferior quadrant of the glenoid cavity, which had an “inverted-pear” appearance. Patients were followed for at least 4.5 years (range, 4.5-14). Serial postoperative radiographs were evaluated. Functional outcomes were assessed using Rowe scores. Results: All grafts showed bony union within 6 months after surgery. The mean Rowe score improved to 84 from a preoperative score of 24. The mean loss of external rotation was 7° compared with the normal shoulder. One subluxation and 1 dislocation occurred after grand mal seizures during follow-up. These 2 patients regained shoulder stability after closed reduction. The remaining patients did not report recurrent instability. All patients resumed daily activities without restricted motion. Conclusion: This technique for open reconstruction is viable for the treatment of recurrent anterior glenohumeral instability with large bony glenoid erosion.

Eighteen symptomatic advanced-stage osteochondritis dissecans (OCD) of the talus (Berndt and Harty stages III 7 and IV 11) in 17 patients were treated with multiple autogenous osteochondral cylindrical grafts. The mean time of follow-up was 36 months (range, 25–49). The average age at surgery was 22.7 years (range, 19–34). The mean size of defect of OCD was 13.6 mm × 7.2 mm. Two or three osteochondral grafts (6 or 7 mm in diameter and 15–20 mm in length) were harvested from the superomedial margin of the ipsilateral knee. A partial osteotomy of the medial malleolus or osteotomy of the distal lateral tibia was performed for all cases. Being evaluated by the Freiburg ankle score, 16 of 18 ankles (88.8%) had excellent and two (11.8%) had good results. “Second-look” arthroscopy of 16 ankles revealed consistency of the osteochondral grafts and congruity between grafts and native cartilage in 14 (87.5%), and a softening or fissuring of the osteochondral graft in two. Our results showed that this procedure provided an effective treatment for a symptomatic advanced-stage OCD of the talus.

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-1β-stimulated human osteoarthritis (OA) chondrocytes remains unknown. Our objectives in this study were to explore the anti-inflammatory effects of genistein on IL-1β-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-1β-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.