Hongsheng Zhan

Triptolide Prevents Bone Destruction in the Collagen-Induced Arthritis Model of Rheumatoid Arthritis by Targeting RANKL/RANK/OPG Signal Pathway

Focal bone destruction within inflamed joints is the most specific hallmark of rheumatoid arthritis (RA). Our previous study indicated that the therapeutic efficiency of triptolide in RA may be due partially to its chondroprotective and anti-inflammatory effects. However, its roles in bone destruction are still unclear. In this study, our data firstly showed the therapeutic effects of triptolide on severity of arthritis and arthritis progression in collagen-induced arthritis (CIA) mice. Then, by micro-CT quantification, triptolide treatment significantly increased bone mineral density, bone volume fraction, and trabecular thickness and decreased trabecular separation of inflamed joints. Interestingly, triptolide treatment could prevent the bone destruction by reducing the number of osteoclasts in inflamed joints, reducing the expression of receptor activator of NF-κB (RANK) ligand (RANKL) and RANK, increasing the expression of osteoprotegerin (OPG), at both mRNA and protein levels, and decreasing the ratio of RANKL to OPG in sera and inflamed joints of CIA mice, which were further confirmed in the coculture system of human fibroblast-like synovial and peripheral blood mononuclear cells. These findings offer the convincing evidence for the first time that triptolide may attenuate RA partially by preventing the bone destruction and inhibit osteoclast formation by regulating RANKL/RANK/OPG signal pathway.

Liver X Receptor α Inhibits Osteosarcoma Cell Proliferation through Up-Regulation of FoxO1

Background: Osteosarcoma is the most common primary bone malignancy of adolescents and young adults. Methods: We analyzed liver X receptor α (LXRα) mRNA expression in 16 pairs of human osteosarcoma tissues and adjacent noncancerous tissues. Moreover, we investigated LXRαs potential role in regulating cell proliferation in Saos-2 and U2OS cells. Results: We found that activation of LXRα, a member of nuclear receptor, was able to inhibit cell proliferation in Saos-2 and U2OS cells. At the molecular level, our results further revealed that expression of tumor suppressor gene, FoxO1, was up-regulated by LXRα activation. LXRα activates FoxO1 transcription through a direct binding on its promoter region. Conclusion: LXRα acts as a tumor suppressor for osteosarcoma, which may offer a new way in molecular targeting cancer treatment.

Ultrasound treatment for accelerating fracture healing of the distal radius. A control study

PURPOSE To investigate the accelerating effects of low-intensity pulse ultrasound stimulation (LIPUS) on the fracture healing of distal radius. METHODS A total of 81 patients with distal radius fracture were randomly divided into two groups: the ultrasound treatment group and the control group. Patients in the ultrasound treatment group were immobilized in a below-elbow cast and received LIPUS treatment 15 min/day, while the control group were immobilized by a plaster support and cast. The patients were followed up every week and took X-ray films. The initial and healed X-ray films and the gray value of fracture site were analyzed by Photoshop software. The effect of reposition was evaluated based upon Steward recommended by Dienst, combining with Aros measuring method. RESULTS Clinical fracture healing time in ultrasound group was significantly shorter than that in the control group (32.04 ± 2.58d vs. 40.75 ± 5.12d, p <0.01). In addition, the grey value changes of fracture sites of the ultrasound group were much higher than that of the control group. The reposition effects of fracture healing had no difference between the two groups (p >0.05). CONCLUSION Low-intensity pulse ultrasound stimulation could accelerate fracture healing of the distal radius and promote local bone formation.

Effectiveness, Medication Patterns, and Adverse Events of Traditional Chinese Herbal Patches for Osteoarthritis: A Systematic Review

Objective. The aim of this study is to systematically evaluate the evidence whether traditional Chinese herbal patches (TCHPs) for osteoarthritis (OA) are effective and safe and analyze their medication patterns. Methods. A systematic literature search was performed using all the possible Medical Subject Headings (MeSH) and keywords from January 1979 to July 2013. Both randomized controlled trials (RCTs) and observational studies were included. Estimated effects were analyzed using mean difference (MD) or relative risk (RR) with 95% confidence intervals (CI) and meta-analysis. Results. 86 kinds of TCHPs were identified. RCTs and controlled clinical trials (CCTs) which were mostly of low quality favored TCHPs for local pain and dysfunction relief. TCHPs, compared with diclofenac ointment, had significant effects on global effectiveness rate (RR = 0.50; 95% CI (0.29, 0.87)). Components of formulae were mainly based on the compounds “Xiao Huo Luo Dan” (Minor collateral-freeing pill) and “Du Huo Ji Sheng Tang” (Angelicae Pubescentis and Loranthi decoction). Ten kinds of adverse events (AEs), mainly consisting of itching and/or local skin rashes, were identified after 3-4 weeks of follow-up. Conclusions. TCHPs have certain evidence in improving global effectiveness rate for OA; however, more rigorous studies are warranted to support their use.

Bufalin Exerts Inhibitory Effects on IL-1β-Mediated Proliferation and Induces Apoptosis in Human Rheumatoid Arthritis Fibroblast-Like Synoviocytes

Rheumatoid arthritis fibroblast-like synoviocytes (RAFLSs) proliferate abnormally and resist apoptosis. Bufalin inhibits cell proliferation and induces apoptosis in human cancer cells. In this study, we explored the effects of bufalin on interleukin-1beta (IL-1β)-induced proliferation and apoptosis of RAFLSs. The cell proliferation and apoptosis were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide assay and annexin V/propidium iodide staining, respectively. Bufalin dose-dependently inhibited IL-1β-induced RAFLS proliferation. Mechanistically, bufalin decreased the activation of mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-κB), both of which are involved in IL-1β-mediated RAFLS proliferation. Moreover, bufalin induced apoptosis and mitochondrial damage of RAFLSs, which was associated with Bcl-2 downregulation, Bax upregulation, mitochondrial cytochrome c release, and enhanced cleavages of caspase-3 and poly-(ADP-ribose) polymerase. Collectively, our results reveal that bufalin suppresses IL-1β-induced proliferation of RAFLSs through MAPK and NF-κB signaling pathways and induces RAFLS apoptosis via the mitochondria-dependent pathway.

Diagnosis and management of knee osteoarthritis: Chinese medicine expert consensus (2015)

Literature review shows that Chinese medicine and other related treatment are still the main stream treatment of knee osteoarthritis. Currently, there is short of handbook guiding Chinese medicine from evidence-based medical evidence, so it is a top priority to develop a clinical guideline from the expert consensus. After several rounds of discussion during the conference and examination by letter, which has collected opinions from nearly one hundred experts, consensus was reached. Nonpharmacologic interventions include health education, medical exercise, acupuncture, massage, acupotomology, and physiotherapy. Pharmacological interventions are as follows. Topical application includes fumigation, application, hot compressed, ironing and iontophoresis with Chinese herbs, etc. Chinese patent medicine for external use includes plaster, ointment, etc. Western medicine for external use mainly includes emulsion, ointment, plaster and embrocation containing nonsteroidal anti-inflammatory drugs (NSAIDs). Intraarticular injection mainly includes sodium hyaluronic acid, chitosan (for injection) with prudent use of glucocorticoid. Chinese herbal medicine and Chinese patent medicine can be taken referring to syndrome differentiation which mainly includes syndromes of qi stagnation and blood stasis, cold dampness, deficiency of Gan (Liver) and Shen (Kidney), deficiency of qi and blood. Western medicine mainly includes analgesic, NSAIDs, diseases modifying drugs. Surgery procedures mainly include joint irrigation, arthroscopic surgery, osteotomy, arthroplasty, etc.

Ovariectomy-induced osteopenia influences the middle and late periods of bone healing in a mouse femoral osteotomy model.

Objective It is known that bone healing was delayed in the presence of osteoporosis in humans. However, due to the complexities of the healing of osteoporotic fractures, animal models may be more appropriate to study the effects of osteoporosis in more details and to test drugs on the fracture repair process. The purpose of this study was to investigate the influence of ovariectomy-induced osteopenia in bone healing in an open femoral osteotomy model, and to test the feasibility of this model for evaluating the healing process under osteopenic conditions. Methods In assessing the effects of osteopenia on fracture healing, ovariectomized mouse models were employed. A mid-shaft femur osteotomy model was also established 3 weeks after ovariectomy as an osteopenic fracture group (OVX group). Femurs were then harvested at 2 weeks and 6 weeks after fracture for X-ray radiography, micro-computed tomography (micro-CT), histology and biomechanical analysis. A sham-operated group (Sham group) was used for comparison. Results The OVX mice had significantly lower BVF, vBMD and TMD in the fracture calluses at 6 weeks (P < 0.05), and similar trend was observed in 2 weeks. Additionally, larger calluses in OVX animals were observed via micro-CT and X-ray, but these did not result in better healing outcomes as determined by biomechanical test at 6 weeks. Histological images of the healing fractures in the OVX mice found forward of broken end resorption and delay of hard callus remodeling. The impaired biomechanical measurements in the OVX group (P < 0.05) were consistent with micro-CT measurements and radiographic scoring, which also indicated delay in fracture healing of the OVX group. Conclusions This study provided evidences that ovariectomy-induced osteopenia impair the middle and late bone healing process once more. These data also supported the validity of the mouse femoral osteotomy model in evaluating the process of bone healing under osteopenic conditions.

Open vs. closed reduction combined with minimally invasive plate osteosynthesis in humeral fractures

Abstract Aim To explore a more effective surgical procedure, the outcomes of closed manipulative reduction (CMR) combined with minimally invasive plate osteosynthesis (MIPO) and conventional open reduction and internal fixation (ORIF) for treating proximal humeral fractures were compared. Material and methods In a retrospective study of patients operated for humerus shaft fractures from April 2008 to July 2011, the outcomes of 33 patients treated with CMR/MIPO were compared with the outcomes of 42 patients treated with ORIF. The fractures were classified, and the incision length, blood transfusion, operating time, as well as the VAS (Visual Analog Scale) pain scores were analyzed. The neck–shaft angles of the proximal humerus were detected, and the postoperative function of the shoulder was evaluated. Results The mean values of incision length, blood transfusion, and VAS pain scores at the 1st and 3rd day after CMR/MIPO and operation time were lower than that of ORIF. The postoperative radiographs verified good position of all screws and satisfactory bone fracture reduction in both groups. Meanwhile, in the ORIF group, nonunion (three cases) and humeral head necrosis (four cases) were detected. Conclusions The MR/MIPO technique showed smaller incisions, easier operation, less blood transfusion and more effective recovery of shoulder joint function for treating proximal humeral fractures than ORIF.

Glucan HBP-A Increase Type II Collagen Expression of Chondrocytes in Vitro and Tissue Engineered Cartilage in Vivo

ObjectiveAlthough chondroprotective activities have been documented for polysaccharides, the potential target of different polysaccharide may differ. The study was aimed to explore the effect of glucan HBP-A in chondrocyte monolayer culture and chondrocytes-alginate hydrogel constructs in vivo, especially on the expression of type II collagen.MethodsChondrocytes isolated from rabbit articular cartilage were cultured and verified by immunocytochemical staining of type II collagen. Chondrocyte viability was assessed after being treated with HBP-A in different concentrations. Morphological status of chondrocytes-alginate hydrogel constructs in vitro was observed by scanning electron microscope (SEM). The constructs were treated with HBP-A and then injected to nude mice subcutaneously. Six weeks after transplantation, the specimens were observed through transmission electron microscopy (TEM). The mRNA expressions of disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTs-5), aggrecan and type II collagen in both monolayer culture and constructs were determined by real time polymerase chain reaction (PCR). The expression of type II collagen and matrix metalloproteinases-3 (MMP-3) in chondrocyte monolayer culture was also tested through Western blot and enzyme linked immunosorbent assay (ELISA), respectively.ResultsMMP-3 secretion and ADAMTs-5 mRNA expression in vitro were inhibited by HBP-A at 0.3 mg/mL concentration. In morphological study, there were significant appearance of collagen in those constructs treated by HBP-A. Accordingly, in both chondrocyte monolayer culture and chondrocytes-alginate hydrogel constructs, the expression of type II collagen was increased significantly in HBP-A group when compared with control group (P<0.001).ConclusionsThe study documented that the potential pharmacological target of glucan HBP-A in chondrocytes monolayer culture and tissue engineered cartilage in vivo may be concerned with the inhibition of catabolic enzymes MMP-3, ADAMTs-5, and increasing of type II collagen expression.