Background: Rheumatoid arthritis (RA) is an autoimmune disease of which the pathogenetic mechanisms are not fully understood. Semaphorin3A (Sema3A) has an immune regulatory role. Neuropilin1 (NRP1), the primary receptor for Sema3A, is also a receptor for vascular endothelial growth factor 165 (VEGF₁₆₅). It has been shown that Sema3A competitively antagonizes VEGF165 signaling. This study investigated whether Sema3A is expressed in synovial tissues, and is associated with disease activity and the histological features of synovial tissues from RA patients.Methods: Human synovial tissues samples were obtained from RA and osteoarthritis (OA) patients. Disease activity of RA patients was calculated using the 28-joint Disease Activity Score based on C-reactive protein (DAS28-CRP). The histological features of RA synovial tissues were evaluated using Rooney’s inflammation scoring system. The localization of Sema3A, VEGF₁₆₅and NRP1 positive cells was immunohistochemically determined in synovial tissues. Expression levels ofSema3A, VEGF-AandNRP1mRNA were determined using quantitative real-time polymerase chain reaction (qPCR).Results: In OA specimens, Sema3A, VEGF₁₆₅and NRP1 proteins were expressed in the synovial lining and inflammatory cells beneath the lining. Immunohistochemistry revealed the protein expression of Sema3A in synovial lining cells was decreased in RA tissues compared with OA samples. qPCR analysis demonstrated a significant reduction ofSema3AmRNA levels in RA synovial tissue samples than in OA and a significant correlation of the ratio ofSema3A/VEGF-AmRNA expression levels with DAS28-CRP (R = −0.449, p = 0.013).Sema3AmRNA levels also correlated with Rooney’s inflammation score, especially in perivascular infiltrates of lymphocytes (R = −0.506, p = 0.004), focal aggregates of lymphocytes (R = −0.501, p = 0.005) and diffuse infiltrates of lymphocytes (R = −0.536, p = 0.002).Conclusions: Reduction of Sema3A expression in RA synovial tissues may contribute to pathogenesis of RA.

We investigated the effect of low‐intensity pulsed ultrasound (LIPUS) on the homing of circulating osteogenic progenitors to the fracture site. Parabiotic animals were formed by surgically conjoining a green fluorescent protein (GFP) mouse and a syngeneic wild‐type mouse. A transverse femoral fracture was made in the contralateral hind limb of the wild‐type partner. The fracture site was exposed to daily LIPUS in the treatment group. Animals without LIPUS treatment served as the control group. Radiological assessment showed that the hard callus area was significantly greater in the LIPUS group than in the control group at 2 and 4 weeks post‐fracture. Histomorphometric analysis at the fracture site showed a significant increase of GFP cells in the LIPUS group after 2 weeks (7.5%), compared to the control group (2.4%) (p < 0.05). The LIPUS group exhibited a significantly higher percentage of GFP cells expressing alkaline phosphatase (GFP/AP) than the control group at 2 weeks post‐fracture (5.9%, 0.3%, respectively, p < 0.05). There was no significant difference in the percentage of GFP/AP cells between the LIPUS group (2.0%) and the control group (1.4%) at 4 weeks post‐fracture. Stromal cell derived factor‐1 and CXCR4 were immunohistochemically identified at the fracture site in the LIPUS group. These data indicate that LIPUS induced the homing of circulating osteogenic progenitors to the fracture site for possible contribution to new bone formation. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:1516–1521, 2012

Background: The changes in synovial fluid biomarkers after intra‐articular injection of hyarulonic acid (IA HA) remain controversial. We investigate the changes in the properties of synovial fluid (SF) and clinical symptoms before the first and fifth IA HA.Methods: A total of 73 patients (73 knees) with symptomatic knee osteoarthritis were treated with five weekly intra‐articular injections of HA and 55 patients (55 knees) were analyzed. The SF total volume, viscosity, and levels of HA, chondroitin 4‐sulfate (C4S), chondroitin 6‐sulfate (C6S), keratin sulfate, and interleukin (IL)‐6 were measured before the first and fifth injections. Clinical evaluations were performed using the American Knee Society score for physician‐based outcome measurements and Knee injury and Osteoarthritis Outcome Score for patient‐based outcome measurements before the first and fifth injections.Results: The SF viscosity and levels of HA were significantly increased, and the total SF volume and levels of chondroitin 4‐sulfate, chondroitin 6‐sulfate, and interleukin‐6 were significantly decreased. The physician‐based and patient‐based outcome scores were improved.Conclusions: Our findings speculate that HA injections significantly modulate levels of intra articular biomarkers which may indicate beneficial effect for articular cartilage and synovium membrane.