BACKGROUND:Wnt signal pathway is involved in the regulation of bone marrow mesenchymal stem cells differentiating into osteoblasts, promotes osteoblasts proliferation and differentiation, inhibits programmed death of osteoblasts, and indirectly affects the function of osteoclasts.
OBJECTIVE:To summarize the relationship between Wnt/β-catenin signal pathway and bone disease.
METHODS:A computer-based online search was performed to find papers published between January 2000 and January 2014 in CNKI database and Elsevier database. The key words were“Wnt/β-catenin, osteoblasts, bone marrow mesenchymal stem cells, osteoarthritis, chondrocytes”in Chinese. Documents concerning the effects of Wnt/β-catenin signal pathway on osteoblasts and bone disease were included.
RESULTS AND CONCLUSION:Wnt signaling pathway is consisted of Wnt/β-catenin signal pathway (Wnt typical signal pathway), Wnt/Ca2+signal pathway and Wnt/planar cellpolarity signal pathway. Wnt signaling pathway is one of the most important regulatory systems that plays a key role in modulating the differentiation, proliferation and programmed celldeath of osteoblasts, osteoclasts and chondrocytes. The role of Wnt signal pathway in patients with rheumatoid arthritis is mediated by osteoblasts. The inhibitory factor of Wnt signal pathway in osteoblasts is upregulated, which reduces the ratio of osteoprotegerin/receptor activating factor ligand, promotes the osteoclasts differentiation and immaturation. The researches addressing the components and effect of Wnt signal pathway are important for the special treatment of bone diseases and the prevention of osteoporosis or other bone diseases.

Objective To investigate the effects of locally and systemically administered alendronate on wear-debris induced osteolysis in vivo. Methods Endotnxin-free titanium particles were injected into rabbit femurs prior to insertion of a non-weight-bearing polymethylmethacrylate plug into the distal femur canal. Then the particles were repeatedly injected into the knee 2, 4 and 6 weeks after the implantation. Alendronate was incorporated into bone cement for local delivery at three different concentrations [0.1, 0.5, and 1.0 weight%(wt%)]. For systemic delivery, alendronate was subcutaneously injected ( 1.0 mg· kg-1·week-1).Results Eight weeks after operation, there was significant evidence of osteolysis surrounding the plug in the control group, while markedly-blocked osteolysis was noted in the local delivery group (0.5 wt% and 1.0 wt%), and the systemic delivery group. It was found that alendronate had improved peri-prosthetic bone mineral density in a dose-effect model. Notably, no significant difference was found between local delivery of 0.5 wt% alendronate and systemic delivery in bone mineral density and implant fixation. Conclusion Alendronate-loaded bone cement (0.5 wt% ) may be as effective as the systemic delivery in inhibiting titanium particle-induced osteolysis.

Objective To evaluate the effects of all intravenous anesthesia and total inhalation anesthesia on left ventricular systolic and diastolic function in elderly patients undergoing intestinal surgery. Methods Forty elderly patients without any history or signs of cardiovascular disease, 23 males and 17 females, aged 65-80 years, ASA physical status Ⅱ or Ⅲ, were randomly allocated into two groups. Maintenance of anesthesia was achieved by propofol-remifentanil respectively (group P) or sevoflurane inhalation (group S). Transesophageal echocardiography was performed as a baseline after intubation. Left ventricular ejection fraction (LVEF), fractional shortening (FS), peak E, E/A, peak E deceleration time (EDT) were measured after anesthesia induction (T0), 10 min after incision (T1), end of surgery (T2), respectively. Results Compared with T0, LVEF, FS, Peak E, E/A of both groups were similar at T1. There were no statistical differences in LVEF and FS between the two groups at T2. However, the value of peak E and E/A of group S at T2 were significantly increased than the baseline T0 and higher than that of group P (P ＜ 0.05). Meanwhile, EDT at T2 in group S was shorter than that at T0 and significant shorter than in group P (P ＜ 0.05). There were two PONV cases in each of the two groups. Conclusion Sevoflurane had a favourable effect on diastolic function in the elderly patients. Furthermore, sevoflurane showed advantage in maintaining hemodynamic stability during the operative period.

Objective:To evaluate the quality of information about bronchial asthma in Chinese Internet Site.Methods:According to the traffic ranking of Alexa website, three Chinese keywords of “bronchial asthma”, “asthma” and “asthma treatment” were searched in two most common Chinese search engines: Baidu and Sohu, and the information quality was evaluated by DISCERN tool. The completeness and accuracy of the information were evaluated according to the “2019 Global Strategy For Asthma Management And Prevention”.Results:A total of 25 websites were obtained. The DISCERN evaluation showed that none of the evaluations had an average score of more than 3.40 points. More than 50% of the information on the websites was incomplete or incorrect, and 4% of the websites contained incorrect information. The website content scores were graded, and the grading results were: excellent 12%, good 40%, fair 36%, poor 12%. The website was evaluated according to the attributes of the owner. Professional websites had better accuracy and comprehensive websites had better comprehensiveness. Pearson correlation analysis showed that the content score was positively correlated with the reliability score, detail score, and total score in DISCERN score ( r=0.58, 0.63, 0.61, all P<0.001). Conclusion:The quality of asthma information on Chinese Internet Site is generally poor.

Osteoarthritis (OA) is a prevalent joint disease with no effective treatment strategies. Aberrant mechanical stimuli was demonstrated to be an essential factor for OA pathogenesis. Although multiple studies have detected potential regulatory mechanisms underlying OA and have concentrated on developing novel treatment strategies, the epigenetic control of OA remains unclear. Histone demethylase JMJD3 has been reported to mediate multiple physiological and pathological processes, including cell differentiation, proliferation, autophagy, and apoptosis. However, the regulation of JMJD3 in aberrant force-related OA and its mediatory effect on disease progression are still unknown. In this work, we confirmed the upregulation of JMJD3 in aberrant force-induced cartilage injury in vitro and in vivo. Functionally, inhibition of JMJD3 by its inhibitor, GSK-J4, or downregulation of JMJD3 by adenovirus infection of sh-JMJD3 could alleviate the aberrant force-induced chondrocyte injury. Mechanistic investigation illustrated that aberrant force induces JMJD3 expression and then demethylates H3K27me3 at the NR4A1 promoter to promote its expression. Further experiments indicated that NR4A1 can regulate chondrocyte apoptosis, cartilage degeneration, extracellular matrix degradation, and inflammatory responses. In vivo, anterior cruciate ligament transection (ACLT) was performed to construct an OA model, and the therapeutic effect of GSK-J4 was validated. More importantly, we adopted a peptide-siRNA nanoplatform to deliver si-JMJD3 into articular cartilage, and the severity of joint degeneration was remarkably mitigated. Taken together, our findings demonstrated that JMJD3 is flow-responsive and epigenetically regulates OA progression. Our work provides evidences for JMJD3 inhibition as an innovative epigenetic therapy approach for joint diseases by utilizing p5RHH-siRNA nanocomplexes.
Cartilage, Articular/pathology* ; Chondrocytes/metabolism* ; Down-Regulation ; Epigenesis, Genetic ; Humans ; Jumonji Domain-Containing Histone Demethylases/metabolism* ; Nuclear Receptor Subfamily 4, Group A, Member 1/metabolism* ; Osteoarthritis/pathology* ; RNA, Small Interfering/pharmacology*