Byakangelicol suppresses TiPs-stimulated osteoclastogenesis and bone destruction via COX-2/NF-κB signaling pathway.

Aseptic loosening (AL) is considered a significant cause of prosthesis revision after arthroplasty and a crucial factor in the longevity of an artificial joint prosthesis. The development of AL is primarily attributed to a series of biological reactions, such as peri-prosthetic osteolysis (PPO) induced by wear particles around the prosthesis. Chronic inflammation of the peri-prosthetic border tissue and hyperactivation of osteoclasts are key factors in this process, which are induced by metallic wear particles like Ti particles (TiPs). In our in vitro study, we observed that TiPs significantly enhanced the expression of inflammation-related genes, including COX-2, IL-1ß and IL-6. Through screening a traditional Chinese medicine database, we identified byakangelicol, a traditional Chinese medicine molecule that targets COX-2. Our results demonstrated that byakangelicol effectively inhibited TiPs-stimulated osteoclast activation. Mechanistically, we found that byakangelicol suppressed the expression of COX-2 and related pro-inflammatory factors by modulating macrophage polarization status and NF-κB signaling pathway. The in vivo results also demonstrated that byakangelicol effectively inhibited the expression of inflammation-related factors, thereby significantly alleviating TiPs-induced cranial osteolysis. These findings suggested that byakangelicol could potentially be a promising therapeutic approach for preventing PPO.

Zero-P and ROI-C implants versus traditional titanium plate with cage to treat cervical spondylotic myelopathy: clinical and radiological results with 5 years of follow-up.

BACKGROUND: Anterior cervical discectomy and fusion (ACDF) is the gold standard for treating cervical spondylotic myelopathy (CSM). While implanting plates in ACDF may increase the risk of complications. Zero-P and ROI-C implants have been gradually applied for CSM. METHODS: 150 patients with CSM were retrospectively analyzed from January 2013 to July 2016. Group A consisted of 56 patients who received traditional titanium plates with cage. 94 patients underwent ACDF using zero-profile implants and were divided into 50 patients with the Zero-P device (Group B) and 44 with the ROI-C device (Group C). Related indicators were measured and compared. The clinical outcomes were evaluated by JOA, VAS, and NDI scores. RESULTS: Compared with group A, group B and C had a less blood loss and shorter operation time. The JOA and VAS scores improved significantly from pre-operative to 3 months postoperative and last follow-up in three groups. The cervical physiological curvature and segmental lordosis at final follow-up were higher than that of pre-operation (p < 0.05). Dysphagia rate, adjacent level degeneration rate, and Osteophyma rate was the highest in group A (p < 0.05). The bone graft fusion was achieved at the final follow-up in three groups. There were no statistical significance in fusion rate and subsidence rate among the three groups. CONCLUSIONS: ACDF with Zero-P or ROI-C implants can also obtain satisfactory clinical outcomes compared to traditional titanium plate with cage after 5 years follow-up. The zero-profile implant devices carry a simple operation, short operation time, less intraoperation blood loss, and incidence of dysphagia.

Structural characteristics and diversity of the rhizosphere bacterial communities of wild Fritillaria przewalskii Maxim. in the northeastern Tibetan Plateau.

Introduction: Fritillaria przewalskii Maxim. is a Chinese endemic species with high medicinal value distributed in the northeastern part of the Tibetan Plateau. F. przewalskii root-associated rhizosphere bacterial communities shaped by soil properties may maintain the stability of soil structure and regulate F. przewalskii growth, but the rhizosphere bacterial community structure of wild F. przewalskii from natural populations is not clear. Methods: In the current study, soil samples from 12 sites within the natural range of wild F. przewalskii were collected to investigate the compositions of bacterial communities via high-throughput sequencing of 16S rRNA genes and multivariate statistical analysis combined with soil properties and plant phenotypic characteristics. Results: Bacterial communities varied between rhizosphere and bulk soil, and also between sites. Co-occurrence networks were more complex in rhizosphere soil (1,169 edges) than in bulk soil (676 edges). There were differences in bacterial communities between regions, including diversity and composition. Proteobacteria (26.47-37.61%), Bacteroidetes (10.53-25.22%), and Acidobacteria (10.45-23.54%) were the dominant bacteria, and all are associated with nutrient cycling. In multivariate statistical analysis, both soil properties and plant phenotypic characteristics were significantly associated with the bacterial community (p < 0.05). Soil physicochemical properties accounted for most community differences, and pH was a key factor (p < 0.01). Interestingly, when the rhizosphere soil environment remained alkaline, the C and N contents were lowest, as was the biomass of the medicinal part bulb. This might relate to the specific distribution of genera, such as Pseudonocardia, Ohtaekwangia, Flavobacterium (relative abundance >0.01), which all have significantly correlated with the biomass of F. przewalskii (p < 0.05). Discussion: F. przewalskii is evidently averse to alkaline soil with high potassium contents, but this requires future verification. The results of the present study may provide theoretical guidance and new insights for the cultivation and domestication of F. przewalskii.

Clinical application of the anterior pelvic wall locking plate (APWLP) in acetabular fractures involving the quadrilateral surface.

BACKGROUND: The management of acetabular quadrilateral surface fractures remains challenging for surgeons, and the treatment options for such fractures remain controversial. Quadrilateral surface surgery is a complex procedure involving combined approaches, and the quality of fracture reduction closely depends upon the surgical procedure, as well as the skill and experience of the surgeon. This study aimed to explore the clinical effects of applying an anterior pelvic wall locking plate (APWLP) through the lateral-rectus approach for treating acetabular fractures involving the quadrilateral surface. METHODS: This retrospective analysis was comprised of 35 patients with acetabular fractures involving the quadrilateral surface who were treated with an APWLP in our hospital between June 2016 and December 2020. The patients included 25 males and ten females, with an average age of 52.45 years. All the patients were exposed through the lateral-rectus approach, six patients were exposed with an additional iliac fossa approach, and the fractures were fixed by combining an APWLP with a reconstruction plate. The Matta imaging standard was used to assess the quality of the fracture reduction, and the final follow-up clinical outcome was classified as excellent (18 points), good (15-17), fair (13-14), or poor (< 13) according to the modified Merle d'Aubigné-Postel scoring standard. RESULTS: All patients successfully completed the operation, and there was no blood vessel or nerve injury during any of the operations. The average follow-up period was 26.11 months. The mean time of resuming full-weight-bearing activities was 12.88 weeks. Hip flexion and extension and internal and external rotation ranges of motion significantly increased over time. At the last follow-up, Matta's imaging evaluation showed that 24 cases were anatomically reduced, seven cases were satisfactory, and four cases were unsatisfactory. The satisfaction rate was 88.6% (31/35). According to the modified Merle d'Aubigné-Postel scoring standard, the hip function was excellent, good, fair, and poor in 23, 6, 4, and 2 cases, respectively. The excellent and good rates represented 82.9% of the total cases (29/35). CONCLUSION: The findings suggest that the APWLP for acetabulum quadrilateral surface fracture achieve good to excellent clinical and radiological outcomes, and an APWLP may be a new treatment option for these fractures involving the quadrilateral surface.

STAT3/IL-6 dependent induction of inflammatory response in osteoblast and osteoclast formation in nanoscale wear particle-induced aseptic prosthesis loosening.

BACKGROUND: Aseptic loosening is the main reason for surgical revision after arthroplasty. Although a series of mechanisms have been explored, a specific therapeutic target is still desired. In the present study, we explored the role of the signal transducer and activator of the transcription (STAT)/interleukin-6 (IL-6) pathway in the induction of the inflammatory response in osteoblast and osteoclast formation during aseptic prosthesis loosening. METHODS: The expression of activated STAT3 was examined in osteoblasts treated with TiAl6V4 nanoparticles (TiPs) from materials used in prosthetics and specimens from particle-induced osteolysis (PIO) animal models. Inflammatory responses associated with the IL-6 family in osteoblasts were identified by Quantitative Real-time PCR. A mimicking coculture system was used to directly determine the number of activated osteoclasts in vitro, and immunohistochemical staining with tartrate-resistant acid phosphatase (TRAP) was used in vivo. CP690,550, an inhibitor of STAT3, was administered to examine the effect of STAT3 on the inflammatory response and osteoclast formation. RESULTS: STAT3 was activated in both nanoparticle-treated osteoblasts and PIO model animals. On the one hand, the activation of STAT3 mediated nanoparticle-induced IL-6-dependent inflammatory responses in osteoblasts. On the other hand, the activation of STAT3 induced receptor activator of nuclear factor kappa B ligand (RANKL) production and stimulated osteoclast formation. The application of the STAT3 inhibitor CP690,550 reduced the production of the IL-6 family and the formation of osteoclasts both in vitro and in vivo. CONCLUSION: STAT3 mediated inflammation-related signalling and osteoclast activation in nanoscale wear particle-induced aseptic loosening. Inhibition of STAT3 by tofacitinib may be a potential treatment for aseptic loosening.

[Soil ecological effect of attapulgite and its application prospect in ecological planting of Chinese materia medica].

The long-term and extensive use of chemical fertilizers and pesticides in the cultivation of Chinese materia medica has resulted in serious soil ecological and environmental problems such as secondary salinization, soil consolidation, soil acidification, continuous cropping obstacles, micro-ecological imbalance, and serious soil pests and diseases in the production areas of Chinese materia medica. Therefore, promoting the ecological planting of Chinese materia medica is the only way for the production of Chinese materia medica. Attapulgite(ATP) is a kind of water-rich magnesium-rich aluminosilicate clay mineral with layered and chain structure. It has abundant reserves in China, possesses nano-material properties, strong adsorption and ion exchange properties, and has huge high value utilization space. ATP and its functional products have the potential of water and fertilizer conservation, regulating soil structure and micro-ecology, and are widely used in ecological planting of Chinese materia medica. This paper reviews the resource distribution, structural characteristics, the research and application progress in soil ecological effects of ATP, and prospects the application prospects of it in the ecological planting of Chinese materia medica.

Hydrogen sulfide protects against particle-induced inflammatory response and osteolysis via SIRT1 pathway in prosthesis loosening.

Wear debris-induced osteolysis and ensuing aseptic loosening is the main cause of implant failure and revision surgery. Wear debris-induced inflammatory response plays key roles in peri-implant osteolysis. Recently, substantial of evidence suggests that hydrogen sulfide (H2 S), the third gasotransmitter, is a critical player regulating inflammation. However, the role and therapeutic potential of H2 S in wear debris-induced inflammation and osteolysis remains to be defined. In the present study, we investigated the effect of H2 S on wear debris-induced pro-inflammatory cytokines expression and osteolysis in vitro and in vivo. With a slow-releasing H2 S donor GYY4137, our study demonstrated that H2 S attenuated wear debris-induced osteolysis and osteoclastogenesis in murine calvaria resorption models. The expression of tumor necrosis factor-alpha (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) that stimulated by wear particles were significantly reduced by GYY4137. Further, the level of sirtuin 1 (SIRT1), which possesses anti-inflammation property, was examined in vivo and in macrophages. And we found that wear debris decreased the expression of SIRT1. Cotreated macrophages with GYY4137 in part reversed the decline of SIRT1. More importantly, with the SIRT1 recombinant lentivirus and small interfering RNAs (siRNA) against SIRT1, our data indicated that SIRT1 mediated the inhibitory effects of GYY4137 on wear debris-induced inflammation. Collectively, these results suggested that exogenous H2 S production (via H2 S donors) may represent a potential approach for the treatment of wear particle-induced osteolysis.

[Analysis of commercial grades of Schisandrae Sphenantherae Fructus based on schisantherin].

Schisandrae Sphenantherae Fructus, from different producing areas, were collected and divided into three grades. The moisture content and total ash were determined on the basis of the pharmacopoeia method, and schisantherin was determined by UPLC. The study is aimed to find the commercial specifications and grades of Schisandrae Sphenantherae Fructus based on schisantherin content. The results showed that the content of water, total ash and schisantherin of Schisandrae Sphenantherae Fructus from different producing areas qualified. There was no significant difference between different grades of schisandrin content, but the second-class were the highest, first-class and third-class were lower. It means that schisandrin content is not positive correlation to commercial grade. The study will be helpful to the production, management and clinical practice of Schisandrae Sphenantherae Fructus.

Proanthocyanidins Attenuation of H2O2-Induced Oxidative Damage in Tendon-Derived Stem Cells via Upregulating Nrf-2 Signaling Pathway.

Proanthocyanidins (PCs) have shown inhibition of oxidative damage by improving Nrf-2 expression in many tissues. However, the cytoprotective effects of PCs on H2O2-induced tendon damage have not been verified. The current study was aimed at assessing the cytoprotection of PCs on the oxidative cellular toxicity of tendon-derived stem cells (TDSCs) induced by H2O2. The TDSCs were isolated from patellar tendons of Sprague Dawley (SD) rats, and the cells after third passage were used for subsequent experiments. The isolated cells were identified by flow cytometry assay and multidifferentiation potential assay. Cell Counting Kit-8 assay was performed to examine cell viability. Real-Time PCR and Western Blot were employed to, respectively, assess the mRNA and protein expressions of Nrf-2, GCLM, NQO-1, and HO-1. PCs significantly improved the cell viability of TDSCs. Furthermore, H2O2 upregulated Nrf-2, GCLM, NQO-1, and HO-1 without significant difference, while the proteins expressions were increased with significant difference in PCs group and PCs + H2O2 cotreated group. All the findings indicated that PCs could protect against the oxidative damage induced by H2O2 in TDSCs, and the cytoprotective effects might be due to the ability of PCs to activate the expressions of GCLM, HO-1, and NQO-1 via upregulating Nrf-2 signaling pathway.

[Prediction of the potential distribution of Tibetan medicinal Lycium ruthenicum in context of climate change].

To predict the suitable distribution patterns of Lycium ruthenicum in the present and future under the background of climate change, and provide reference for the resources sustainable utilization and GAP standardized planting. The software of Maxent and ArcGis was used to predict the potential suitable regions and grades of L. ruthenicum in China based on the 149 distribution information, climate data of contemporary (1950-2000) and future (20-80 decade of 21 century), and considering of three greenhouse gaseous emission scenario. The results showed that：the suitable distribution regions of L. ruthenicum are mainly concentrated in Xinjiang, Qinghai, Gansu, Neimenggu, and Ningxia province in present. In addition, Shaanxi, Shanxi and Xizang are also distribution regions.The suitable distribution area of L. ruthenicum is 284.506 949×104 km2, accounted for 29.6% of the land area of China.The relatively stable area of the suitable regions accounted for 25.2% of the total suitable region area.Under the background of climate change, compared with contemporary, the total area of suitable region is reducing and moderately suitable area is increasing at different degree at the 20, 30, 40, 50, 60, 70, 80 decade of 21 century. Climate change both can change the total area of suitable regions and habitat suitability of L. ruthenicum. It could provide a strategic guidance for protection, development and utilization of L. ruthenicum though the prediction of potential suitable regions distribution of L. ruthenicum based on the mainly factor of climate change.

Probiotics protect mice from CoCrMo particles-induced osteolysis.

Wear particle-induced inflammatory osteolysis is the primary cause of aseptic loosening, which is the most common reason for total hip arthroplasty (THA) failure in the med- and long term. Recent studies have suggested an important role of gut microbiota (GM) in modulating the host metabolism and immune system, leading to alterations in bone mass. Probiotic bacteria administered in adequate amounts can alter the composition of GM and confer health benefits to the host. Given the inflammatory osteolysis that occurs in wear debris-induced prosthesis loosening, we examined whether the probiotic Lactobacillus casei could reduce osteolysis in a mouse calvarial resorption model. In this study, L. casei markedly protected mice from CoCrMo particles (CoPs)-induced osteolysis. Osteoclast gene markers and the number of osteoclasts were significantly decreased in L. casei-treated mice. Probiotic treatment decreased the M1-like macrophage phenotype indicated by downregulation of tumor necrosis factor α (TNF-α), interleukin (IL)-6 and inducible nitric oxide synthase (iNOS) and increased the M2-like macrophage phenotype indicated by upregulation of IL-4, IL-10 and arginase. Collectively, these results indicated that the L. casei treatment modulated the immune status and suppressed wear particle-induced osteolysis in vivo. Thus, probiotic treatment may represent a potential preventive and therapeutic approach to reduced wear debris-induced osteolysis.

Enhanced Uptake of Fe3O4 Nanoparticles by Intestinal Epithelial Cells in a State of Inflammation.

Fe3O4 nanoparticles (Fe3O4 NPs) have been used for medical and drug applications, although the mechanisms of cellular uptake and transport need to be further evaluated under inflammatory conditions. In the present study, we investigated the uptake of Fe3O4 NPs (20, 50, 100, and 200 nm) by intestinal epithelial cells under inflammatory conditions via the light scattering of flow cytometry and inductively coupled plasma mass spectrometry (ICP-MS) techniques. The results of the correlation analysis indicated that the uptake ratios of Fe3O4 NPs by intestinal epithelial cells under inflammatory conditions were higher than those under the control conditions. The transportation ratios of NPs by inflammatory Caco-2 cells increased almost 0.8-1.2 fold compared to the control. The internalization of the Fe3O4 NPs in Caco-2 cells was mediated by clathrin-related routes in both the control and an interleukin-1ß (IL-1ß)-induced inflammatory condition. The level of mRNA of clathrin expressed in Caco-2 cells that were stimulated by IL-1ß was almost three times more than the control. Consistently with the mRNA expression, the level of protein in the clathrin was upregulated. Additionally, it was verified for the first time that the expression of clathrin was upregulated in IL-1ß-stimulated Caco-2 cells. Collectively, these results provided a further potential understanding about the mechanism of Fe3O4 NPs' uptake by intestinal epithelial cells under inflammatory conditions.

The metal nanoparticle-induced inflammatory response is regulated by SIRT1 through NF-κB deacetylation in aseptic loosening.

Aseptic loosening is the most common cause of total hip arthroplasty (THA) failure, and osteolysis induced by wear particles plays a major role in aseptic loosening. Various pathways in multiple cell types contribute to the pathogenesis of osteolysis, but the role of Sirtuin 1 (SIRT1), which can regulate inflammatory responses through its deacetylation, has never been investigated. We hypothesized that the downregulation of SIRT1 in macrophages induced by metal nanoparticles was one of the reasons for osteolysis in THA failure. In this study, the expression of SIRT1 was examined in macrophages stimulated with metal nanoparticles from materials used in prosthetics and in specimens from patients suffering from aseptic loosening. To address whether SIRT1 downregulation triggers these inflammatory responses, the effects of the SIRT1 activator resveratrol on the expression of inflammatory cytokines in metal nanoparticle-stimulated macrophages were tested. The results demonstrated that SIRT1 expression was significantly downregulated in metal nanoparticle-stimulated macrophages and clinical specimens of prosthesis loosening. Pharmacological activation of SIRT1 dramatically reduced the particle-induced expression of inflammatory cytokines in vitro and osteolysis in vivo. Furthermore, SIRT1 regulated particle-induced inflammatory responses through nuclear factor kappa B (NF-κB) acetylation. Thus, the results of this study suggest that SIRT1 plays a key role in metal nanoparticle-induced inflammatory responses and that targeting the SIRT1 pathway may lead to novel therapeutic approaches for the treatment of aseptic prosthesis loosening.

Specifically Formed Corona on Silica Nanoparticles Enhances Transforming Growth Factor ß1 Activity in Triggering Lung Fibrosis.

A corona is a layer of macromolecules formed on a nanoparticle surface in vivo. It can substantially change the biological identity of nanomaterials and possibly trigger adverse responses from the body tissues. Dissecting the role of the corona in the development of a particular disease may provide profound insights for understanding toxicity of nanomaterials in general. In our present study, we explored the capability of different silica nanoparticles (SiNPs) to induce silicosis in the mouse lung and analyzed the composition of coronas formed on these particles. We found that SiNPs of certain size and surface chemistry could specifically recruit transforming growth factor ß1 (TGF-ß1) into their corona, which subsequently induces the development of lung fibrosis. Once embedded into the corona on SiNPs, TGF-ß1 was remarkably more stable than in its free form, and its fibrosis-triggering activity was significantly prolonged. Our study meaningfully demonstrates that a specific corona component on a certain nanoparticle could initiate a particular pathogenic process in a clinically relevant disease model. Our findings may shed light on the understanding of molecular mechanisms of human health risks correlated with exposure to small-scale substances.

Expression of XBP1s in fibroblasts is critical for TiAl6 V4 particle-induced RANKL expression and osteolysis.

Wear particle-induced osteolysis is a major cause of aseptic loosening, which is one of the most common reasons for total hip arthroplasty (THA) failure. Previous studies have shown that the expression of Receptor activation of nuclear factor (NF)-kB (RANKL) by fibroblasts in periprosthetic membrane played a crucial role in wear particle-induced osteolysis. However, the underlying mechanism of RANKL expression remains largely unknown. In the present study, we investigated the effect of TiAl6 V4 particle (TiPs)-induced XBP1s (spliced form of X-box binding protein 1) on RANKL expression and osteoclastogenesis both in vitro and in vivo. The levels of XBP1s in peri-implant membrane, animal models, and TiPs-stimulated fibroblasts were determined by western blots. To assess the effect of XBP1s on RANKL expression, fibroblasts were treated with both a small interfering RNA (siRNA) and an inhibitor of XBP1 prior to exposure to TiPs. The effect of XBP1s on osteoclasts formation was determined by tartrate-resistant acid phosphatase (TRAP) staining in vitro osteoclastogenesis assay and in animal models. The resorption of bone was assessed by micro-computed tomography (micro-CT) with three-dimensional reconstruction. Our results demonstrated that XBP1s was activated in periprosthetic membrane, mouse calvaria models, and TiPs-stimulated human synovial fibroblasts. Further, inhibition of XBP1s decreased the expression of RANKL and osteoclasts formation in vitro. In mouse calvaria models, both of the osteoclastogenesis and osteolysis were inhibited XBP1s inhibitor. Our results suggested that XBP1s mediated TiPs-induced of RANKL expression in fibroblasts, and down regulating XBP1s may represent a potential therapy for wear particle-induced osteolysis. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:752-759, 2017.

SIRT1 protects osteoblasts against particle-induced inflammatory responses and apoptosis in aseptic prosthesis loosening.

We hypothesized that SIRT1 downregulation in osteoblasts induced by wear particles was one of the reasons for particle-induced osteolysis (PIO) in total joint arthroplasty failure. In the present study, the expression of SIRT1 was examined in osteoblasts treated with TiAl6V4 particles (TiPs) and CoCrMo particles (CoPs) from materials used in prosthetics and specimens from PIO animal models. To address whether SIRT1 downregulation triggers inflammatory responses and apoptosis in osteoblasts, the effect of a SIRT1 activator, resveratrol on the expression of inflammatory cytokines and apoptosis in particle-treated osteoblasts was tested. The results demonstrated that SIRT1 expression was significantly downregulated in particle-treated osteoblasts and PIO animal models. Both pharmacological activation and overexpression of SIRT1 dramatically reduced the particle-induced expression of inflammatory cytokines and osteoblast apoptosis through NF-κB and p53 signaling, respectively. Furthermore, in PIO animal models, resveratrol significantly reduced the severity of osteolysis. Collectively, the results of the present study indicated that SIRT1 plays a vital role in the pathogenesis of aseptic loosening, and further treatment targeted at SIRT1 possibly lead to novel approaches for prevention of aseptic prosthesis loosening. STATEMENT OF SIGNIFICANCE: Aseptic loosening is the most common cause of total hip arthroplasty (THA) and total knee arthroplasty (TKA) failure and revision surgery. However, there is still no effective therapeutic target in the clinical treatment. Besides, the underlying mechanism of aseptic loosening is largely unknown. The result of our study indicated that SIRT1 has the ability to effectively regulate the wear particle-induced inflammatory responses, apoptosis, osteolysis in particle-stimulated osteoblasts and particle-induced osteolysis animal models. Our study provides a potential target for the prevention and treatment of aseptic loosening and further investigated the underlying mechanism of aseptic loosening, which may make contribution to decrease the incidence of THA and TKA failure in the clinical practice.

TiAl6V4 particles promote osteoclast formation via autophagy-mediated downregulation of interferon-beta in osteocytes.

Wear debris-induced osteolysis is the leading cause of aseptic loosening, which is the most common reason for total hip arthroplasty (THA) failure in the medium and long term. Although osteocytes are the most abundant cells in bone and make direct contact with implants, the interaction between osteocytes and wear debris remains largely unknown. In the present study, we investigated the effect of TiAl6V4 alloy particles (TiPs) on osteocytes and the subsequent effects on osteoclast formation. Our study demonstrated that osteocyte-conditioned medium (CM) inhibited osteoclast differentiation from bone marrow monocytes (BMMs) to osteoclasts. However, TiPs attenuated this inhibitory effect. The expression of several osteoclastogenesis-associated factors, including receptor activator of nuclear factor-kappaB ligand (RANKL), osteoprotegerin (OPG), nitric oxide (NO) and interferon-beta (IFN-ß), was examined, and we found that TiPs markedly decreased the expression of IFN-ß, but not the other factors. In an osteoclastogenesis assay, our results suggested that the downregulation of IFN-ß mediated the stimulatory effect of TiPs on osteoclastogenesis. Additional evidence suggested that TiPs decreased the expression of IFN-ß in osteocytes via macroautophagy (hereinafter referred to as "autophagy"). Moreover, inhibiting autophagy with Atg5 siRNA prevented the increase in osteoclastogenesis induced by TiPs. Collectively, these results suggested a possible mechanism underlying wear debris-induced osteolysis. STATEMENT OF SIGNIFICANCE: For the first time, our study demonstrated that Ti-alloy particles attenuated the inhibitory effect of osteocytes-conditioned medium on osteoclast formation. With an osteoclastogenesis assay, we found that the downregulation of IFN-ß in osteocytes mediated the promoting effect of TiPs on osteoclast formation. Furthermore, our results suggested that TiPs-induced autophagy mediated the downregulation of IFN-ß in osteocytes. Inhibition of autophagy recovered the expression of IFN-ß and ameliorated the promoting effect of TiPs on osteoclast formation. Collectively, these findings suggest a possible mechanism underlying wear debris-induced osteolysis and identified autophagy inhibition in osteocytes as a potential therapeutic approach for wear debris induced osteolysis.

[Survey and protective utilization of Lycium ruthenicum resources distributed in middle and lower reaches of Heihe river].

This study was aimed to investigate the qualitative and quantitative distributions of Lycium ruthenicum resources in the middle and lower reaches of Heihe River, for providing scientific evidence for the protective utilization of the resources in the corresponding geographic region. The outdoor sample plot and quadrat survey, literature search, sample collection, in-house identification and classification were performed by route surveying and visiting to the local natives and/or herb farmers based on the current distribution data of the L. ruthenicum resources in the middle and lower reaches of Heihe River. The distributive pattern of the resources was analyzed using ArcGIS program. The data regarding the category/distributed area and the genetic resources of the L. ruthenicum were collected. The data collected in this study may provide the scientific evidence for the protective utilization of the L. ruthenicum resources in the corresponding geographic region, allowing for the avoidance of the ecological environment from being damaged by improper utilization.

Autophagy mediated TiAl6V4 particle-induced peri-implant osteolysis by promoting expression of TNF-α.

Peri-prosthetic osteolysis and the consequent aseptic loosening constitute the most common reason for total joint arthroplasty failure and surgical revision. Although numerous studies suggest that pro-inflammatory cytokines induced by wear particles is involved in the pathological process of aseptic loosening, the underlying mechanism linking wear particles to pro-inflammatory cytokines remains to be illustrated. In the present study, we investigated the effect of autophagy on TNF-α secretion induced by TiAl6V4 particles (TiPs) in macrophages and in a calvarial resorption animal model. Our study demonstrated that TiPs activated autophage in macrophages and particle-induced osteolysis animal models as well as periprosthetic membranes of patients with aseptic loosening. The autophagy inhibitor 3-MA (3-methyladenine) could dramatically reduce TiPs-induced TNF-α expression both in macrophages and in membranes from animal models. Furthermore, inhibition of autophagy with 3-MA ameliorated the severity of osteolysis in PIO animal models. Collectively, these results suggest that autophagy plays a key role in TiPs-induced osteolysis by promoting TNF-α expression and that blocking autophagy may represent a potential therapeutic approach for treating particle-induced peri-implant osteolysis.

Autophagy mediated CoCrMo particle-induced peri-implant osteolysis by promoting osteoblast apoptosis.

Wear particle-induced osteolysis is the leading cause of aseptic loosening, which is the most common reason for THA (total hip arthroplasty) failure and revision surgery. Although existing studies suggest that osteoblast apoptosis induced by wear debris is involved in aseptic loosening, the underlying mechanism linking wear particles to osteoblast apoptosis remains almost totally unknown. In the present study, we investigated the effect of autophagy on osteoblast apoptosis induced by CoCrMo metal particles (CoPs) in vitro and in a calvarial resorption animal model. Our study demonstrated that CoPs stimulated autophagy in osteoblasts and PIO (particle-induced osteolysis) animal models. Both autophagy inhibitor 3-MA (3-methyladenine) and siRNA of Atg5 could dramatically reduce CoPs-induced apoptosis in osteoblasts. Further, inhibition of autophagy with 3-MA ameliorated the severity of osteolysis in PIO animal models. Moreover, 3-MA also prevented osteoblast apoptosis in an antiautophagic way when tested in PIO model. Collectively, these results suggest that autophagy plays a key role in CoPs-induced osteolysis and that targeting autophagy-related pathways may represent a potential therapeutic approach for treating particle-induced peri-implant osteolysis.