Curcumin plays an anti-osteoporosis role by inhibiting NF-κB signaling pathway to reduce oxidative stress damage to osteogenesis / 中国药理学通报

Aim To investigate the mechanism of curcumin inhibition of oxidative stress on osteogenic differentiation and its dose-dependent anti-osteoporosis effect. Methods Cellular oxidative stress models were used, different concentrations of curcumin were added to determinethebone formation markers, and the potential signaling pathways involvedwere detected. Meanwhile, the mouse model of osteoporosis ( ovariecto- mized, 0VX) was used to confirm its effect against osteoporosis. Results In vitro experiments found that low concentrations of curcumin (1-10 μmol · L

A new target for improving osteoporosis with eldecalcitol—Mini-modeling bone formation / 中华内分泌代谢杂志

As a basic anti-osteoporosis drug, active vitamin D mainly promotes intestinal absorption of calcium and phosphorus, inhibits the release of parathyroid hormone, and maintains normal blood calcium and phosphorus levels, thus ensuring bone health. Eldecalcitol(ED-71), a novel derivative of active vitamin D, was approved for clinical treatment of osteoporosis in Japan in 2011. Eldecalcitol not only improves intestinal calcium absorption and inhibits osteoclast differentiation, but also effectively promotes "mini-modeling" bone formation-focal bone formation that is independent of osteoclastic bone resorption, elevating trabecular continuity and increasing the thickness of weak trabeculae, thereby repairing the microinjury of bone tissue.

Melatonin attenuates bone resorption induced by acute sleep deprivation in growing rats / 中华内分泌代谢杂志

Objective:To explore the changes of bone turnover markers induced by sleep deprivation (SD) and the effect of melatonin supplementation on the bone turnover status.Methods:Six-week-old Wistar male rats were divided into SD, normal control (NC), and melatonin supplementation (SD+ MT) groups. Acute SD model was established using a modified multi-level bench method. The bone turnover markers, corticosterone, and melatonin in serum as well as Cathepsin K(CTSK) mRNA expression in bone tissue were tested.Results:Acute SD disrupted the balance between bone formation and bone absorption evidenced by rapid decreased serum procollagen type Ⅰ N-terminal propeptide (PⅠNP) levels and increased β cross-linked C-telopeptide of type Ⅰ collagen (β-CTX) levels ( P=0.003) from 24 h to 72 h. The exogenous melatonin treatment decreased β-CTX [(512.4±95.8) ng/mL vs (696.0±76.5) ng/mL, P=0.004] and the osteoclast-related gene CTSK mRNA level after 72 h SD. Conclusions:Acute SD accelerates bone resorption, which could be partially alleviated by melatonin supplementation.

Mechanism of microRNA-30d-5p regulating osteogenic differentiation of bone marrow stromal cells through glucose-regulated 78 / 解剖学报

Objective To investigate the effect of microRNA(miR)-30d-5p on osteogenic differentiation and apoptosis of bone marrow stromal cells and its mechanism. Methods Bone marrow stromal cells were divided into miR-30d-5p overexpression negative control group, miR-30d-5p overexpression group, miR-30d-5p inhibition negative control group and miR-30d-5p inhibition group. Alkaline phosphatase (ALP) staining was used to identify osteogenesis, alizarin red staining was used to detect calcium nodules precipitation, and TUNEL was used to detect apoptosis. mRNA and protein expression levels were detected by Real-time PCR and Western blotting, and the potential binding sites of miR-30d-5p were predicted by the bioinformatics analysis website Targetscan 7.1. Results After miR-30d-5p overexpression, osteogenic differentiation ability, and mineralization ability of the cells decreased (P<0.05), while apoptosis level increased (P< 0.05). The expression of glucoregulatory protein 78 (GRP78) and osteogenic specific transcription factor Runt related transcription factor 2(RUNX2) decreased significantly (P<0.05). However, miR-30d-5p inhibitor-treated the cells with increased osteogenic differentiation and mineralization ability (P < 0.05), and apoptosis level decreased (P < 0.05). GRP78 and RUNX2 protein levels increased (P<0.05). The miR-30d-5p binding site was located at 142-148 bp of the 3'UTR of the GRP78 gene. Conclusion MiR-30d-5p inhibits osteogenic differentiation and promotes apoptosis of bone marrow stromal cells by down-regulating the expression of GRP78 protein.

Research progress on anterior alveolar bone changes after orthodontic treatment involving extractions / 口腔疾病防治

@#It has been traditionally believed that a 1:1 cortical bone remodeling/tooth movement ratio has been preserved during orthodontic treatment for tooth movement, with the alveolar bone on the tension side growing and the alveolar bone on the pressure side resorbing to maintain the balance of the alveolar bone. However, recent studies have shown that alveolar bone loss has been found in patients who have undergone orthodontic treatment, suggesting that the alveolar bone does not change as the teeth change over time. Whether the morphology of the alveolar bone will change when the anterior teeth are moved has been the clinical focus. The changes of anterior alveolar bone in patients who have undergone tooth extraction after orthodontic treatment were summerized by literature review in this paper. The results of the review showed that the alveolar bone at the lingual/palatal root-cervical site of the anterior root is more prone to bone loss after extensive movement of the anterior teeth. With the development of imaging technology, CBCT is now more commonly used for analysis instead of two-dimensional images for measurement, as its results are more accurate. However, there are few multifactorial studies in which CBCT has been used to assess the morphological changes in the alveolar bone. The focus of future research is to compare the long-term changes in the anterior alveolar bone of patients of different ages based on three-dimensional imaging, and to study the correlation between different skeletal features, tooth movement patterns and alveolar bone remodeling.

Effect of Erxian Decoction-containing serum on H_2O_2-induced proliferation and osteogenic differentiation of MC3T3-E1 cells via BK channels / 中国中药杂志

This study aimed to investigate the effects of Erxian Decoction(EXD)-containing serum on the proliferation and osteogenic differentiation of MC3T3-E1 cells under oxidative stress through BK channels. The oxidative stress model was induced in MC3T3-E1 cells by H_2O_2, and 3 mmol·L~(-1) tetraethylammonium(TEA) chloride was used to block the BK channels in MC3T3-E1 cells. MC3T3-E1 cells were divided into a control group, a model group, an EXD group, a TEA group, and a TEA+EXD group. After MC3T3-E1 cells were treated with corresponding drugs for 2 days, 700 μmol·L~(-1) H_2O_2 was added for treatment for another 2 hours. CCK-8 assay was used to detect cell proliferation activity. The alkaline phosphatase(ALP) assay kit was used to detect the ALP activity of cells. Western blot and real-time fluorescence-based quantitative PCR(RT-qPCR) were used to detect protein and mRNA expression, respectively. Alizarin red staining was used to detect the mineralization area of osteoblasts. The results showed that compared with the control group, the model group showed significantly blunted cell proliferation activity and ALP activity, reduced expression of BK channel α subunit(BKα), collagen Ⅰ(COL1), bone morphogenetic protein 2(BMP2), osteoprotegerin(OPG), and phosphorylated Akt, decreased mRNA expression levels of Runt-related transcription factor 2(RUNX2), BMP2, and OPG, and declining area of calcium nodules. EXD-containing serum could significantly potentiate the cell proliferation activity and ALP activity, up-regulate the protein expression of BKα, COL1, BMP2, OPG, and phosphorylated Akt, and forkhead box protein O1(FoxO1), promote the mRNA expression of RUNX2, BMP2, and OPG, and enlarge the area of calcium nodules. However, BK channel blockage by TEA reversed the effects of EXD-containing serum in promoting the protein expression of BKα, COL1, BMP2, OPG, and phosphorylated Akt and FoxO1, increasing the mRNA expression of RUNX2, BMP2, and OPG, and enlarging the area of calcium nodules. EXD-containing serum could improve the proliferation activity, osteogenic differentiation, and mineralization ability of MC3T3-E1 cells under oxidative stress, which might be related to the regulation of BK channels and downstream Akt/FoxO1 signaling pathway.

Suppressing STAT3 activation impairs bone formation during maxillary expansion and relapse

Abstract Objectives The mid-palatal expansion technique is commonly used to correct maxillary constriction in dental clinics. However, there is a tendency for it to relapse, and the key molecules responsible for modulating bone formation remain elusive. Thus, this study aimed to investigate whether signal transducer and activator of transcription 3 (STAT3) activation contributes to osteoblast-mediated bone formation during palatal expansion and relapse. Methodology In total, 30 male Wistar rats were randomly allocated into Ctrl (control), E (expansion only), and E+Stattic (expansion plus STAT3-inhibitor, Stattic) groups. Micro-computed tomography, micromorphology staining, and immunohistochemistry of the mid-palatal suture were performed on days 7 and 14. In vitro cyclic tensile stress (10% magnitude, 0.5 Hz frequency, and 24 h duration) was applied to rat primary osteoblasts and Stattic was administered for STAT3 inhibition. The role of STAT3 in mechanical loading-induced osteoblasts was confirmed by alkaline phosphatase (ALP), alizarin red staining, and western blots. Results The E group showed greater arch width than the E+Stattic group after expansion. The differences between the two groups remained significant after relapse. We found active bone formation in the E group with increased expression of ALP, COL-I, and Runx2, although the expression of osteogenesis-related factors was downregulated in the E+stattic group. After STAT3 inhibition, expansive force-induced bone resorption was attenuated, as TRAP staining demonstrated. Furthermore, the administration of Stattic in vitro partially suppressed tensile stress-enhanced osteogenic markers in osteoblasts. Conclusions STAT3 inactivation reduced osteoblast-mediated bone formation during palatal expansion and post-expansion relapse, thus it may be a potential therapeutic target to treat force-induced bone formation.

Effect and mechanism of serotonin-selective reuptake inhibitor on bone metabolism / 中国药房

Serotonin-selective reuptake inhibitor （SSRI） is the first-line drug for treating depression. SSRI mainly include fluoxetine， paroxetine， sertraline， fluvoxamine， citalopram and escitalopram， etc. SSRI has dual impact on bone metabolism. Short- term use of SSRI may have a positive impact on bone， but long-term use may lead to bone problems. This article summarizes the effects and mechanisms of SSRI on bone metabolism， indicating that SSRI can affect bone formation， bone resorption， mesenchymal stem cell differentiation， and regulate the expression of inflammatory cytokines. The impact of SSRI on bone metabolism can be achieved by affecting classical signaling pathways such as cAMP/PKA/CREB， Wnt/β-catenin， BMP/Smad， OPG/RANKL/RANK， and through centrally mediated effects.

Aqueous extract of freeze-dried Protaetia brevitarsis larvae promotes osteogenesis by activating β-catenin signaling

Objective: To investigate the effect of an aqueous extract of Protaetia brevitarsis (AEPB) on osteogenesis using preosteoblast MC3T3-E1 cells and zebrafish larvae. Methods: Flow cytometric analysis was used to measure the cytotoxicy. Alkaline phosphatase activity was detetmined using p-nitrophenyl phosphate as a substrate. Calcium deposition was detected using alizarin red staining along with osteogenic marker expression in preosteoblast MC3T3E1 cells. In addition, vertebral formation in zebrafish larvae was detected using calcein staining and osteogenic gene expression. Results: AEPB highly promoted the expression of osteogenic markers including runt-related transcription factor 2, osterix, and alkaline phosphatase, along with elevated levels of mineralization in MC3T3-E1 cells. Moreover, AEPB accelerated vertebral formation in zebrafish larvae accompanied by upregulated expression of osteogenic genes. FH535, an inhibitor of Wnt/β-catenin, suppressed AEPB-induced osteogenic gene expression and vertebral formation, indicating that AEPB stimulates osteogenesis by activating the Wnt/β-catenin signaling pathway. Conclusions: AEPB stimulates osteoblast differentiation and bone formation by activating β-catenin. Therefore, AEPB is a promising material that induces osteogenesis, and is useful for the treatment of bone resorption diseases.

Research on mechanism of salidroside activating HIF-1 a signaling pathway to promote MOB proliferation / 中国药理学通报

Aim To explore the effeet of salidroside (SAL) on proliferation of osteoblasts and its possible mechanism by using mouse primary osteoblasts ( MOB) as the research object.Methods Alkaline phosphatase ( ALP) staining was used to identify the extracted primary cells.MTT was used to detect the effect of SAL on the proliferation.RT-PCR, Western blot, ELISA were used to investigate the molecular mechanism of SAL.Results The extracted cells generated black-brown deposits by ALP staining, which were shown to be osteoblasts clearly.SAL promoted the pro liferation of MOB.Meanwhile, SAL could up-regulate the mRNA and protein expression levels of hypoxia-inducible factor-lcx ( HIF-1 ex), vascular endothelial growth factor ( VEGF ) , angiopoietin-like protein 4 (ANGPTL4) and interleukin 6 ( IL-6 ) , which were down-regulated by using the HIF-lex blocker YC-1.Conclusions SAL could promote the proliferation of MOB through HIF-1 a/VEGF, ANGPTL4, IL-6 signaling pathway.

Advances in mechanisms for ankylosing spondylitis and drug regulation / 中国药理学通报

Ankylosing spondylitis(AS)is a chronic inflammatory rheumatic disease, which belongs to the category of autoimmune diseases and is characterized by inflammatory back pain owing to sacroiliitis and other axial arthritis, as well as bone structural damage and pathological new bone formation. Severe joint and extra-joint lesions have caused great inconvenience and pain, from which patients with ankylosing spondylitis suffer a lot. Therefore researchers have paid more attention to the pathogenesis and drug regulation of ankylosing spondylitis in recent years. At present, the universally recognized pathogenesis of AS includes the influence of genetic factors, immune factors and classical osteogenic pathways, all of which are interrelated and synergistically lead to the progression of AS. In view of its pathogenesis, a series of drugs targeting inflammation have been emerging, including tumor necrosis factor inhibitors, interleukin-17/interleukin-23(IL-17/IL-23)monoclonal antibodies and some anti-rheumatism drugs to relieve the symptoms. Moreover, we also herein highlight the therapeutic necessity of targeting pathological osteogenesis.

Histomorphometry evaluation of bone anabolism promoted by prostaglandin E1 and its relation to hypercalcemia / Evaluación histomorfométrica del anabolismo óseo en la reparación promovida por la prostaglandina E1 y su relación con la hipercalcemia

Abstract Background: At present, parathyroid hormone is the only existing anabolic bone therapy but produces hypercalcemia. Prostaglandin E1 (PGE1) has been suggested as a bone anabolic agent that allows bone modeling formation without producing hypercalcemia. This study aimed to corroborate these PGE1 properties. Methods: For 22 days, rabbits (n = 30) were divided into three groups (n = 10 each group) and received intravenous solutions: vehicle (control group), palate disjunction + vehicle (sham group), and palate disjunction + 50 mg of PGE1 (PGE1 group). On days 1, 3, and 22, palatine suture X-rays were taken. On day 22, bone formation markers were analyzed, and the rabbits were sacrificed. Bone palate undecalcified samples were processed. Histomorphometry software was used to analyze bone parameters, and the mineralization front was stained with toluidine blue. Scalloped lines reflect remodeling-based bone formation (RBF), and smooth lines reflect modeling-based formation (MBF). Results: X-rays showed more significant palatal disjunction in the PGE1 group; this group exhibited significant calcitriol serum increments. Hypercalciuria was observed in the PGE1 group, and resorption markers (N-telopeptides) remained stable. Sutural bones in the PGE1 group exhibited significant anabolism in structural parameters. RBF was 20%, and MBF was 6% in the sham group; in the PGE1 group, RBF was 8.6%, and MBF was 17%. In the PGE1 group, mineralization was significantly accelerated, but resorption remained stable. Conclusions: This model suggests that PGE1 favors palate disjunction, calcitriol synthesis, and shortens the mineralization. Therefore, PGE1 is an important bone anabolic molecule predominantly of modeling-based form and no hypercalcemia.

Resumen Introducción: La hormona paratiroidea es la única molécula anabólica ósea, pero ocasiona hipercalcemia. La prostaglandina E1 (PGE1) sugiere ser un anabólico óseo con formación por modelación predominante y generalmente no ocasiona hipercalcemia. El objetivo de este estudio fue corroborar estas propiedades de la PGE1. Métodos: Por 22 días, 30 conejos divididos en tres grupos (n = 10 cada grupo) recibieron una solución por vía intravenosa: vehículo (grupo control), disyunción palatina más vehículo (grupo sham) y disyunción palatina más 50 mg de PGE1 (grupo PGE1). A los días 1, 3 y 22 se obtuvieron radiografías de la sutura palatina. En el día 22 se analizaron los marcadores bioquímicos de formación ósea y se sacrificó a los conejos. Las suturas y los huesos suturales se procesaron sin descalcificar. La evaluación histomorfométrica fue digitalizada y el frente de mineralización ósea se tiñó con azul de toluidina. Las líneas irregulares reflejan resorción (remodelación) y las líneas rectas no resorción (modelación). Resultados: Radiográficamente, la disyunción palatina fue mayor en el grupo PGE1. Este grupo mostró una hipercalcitonemia significativa, pero la calcemia y los marcadores resortivos (N-telopéptidos) se mantuvieron estables. Por histomorfometría, los huesos suturales del grupo PGE1 mostraron anabolismo significativo en parámetros estructurales. En el grupo sham, la remodelación ósea fue del 20% y la modelación fue del 6%; en el grupo PGE1, la remodelación fue del 8.6% y la modelación fue del 17%. En este mismo grupo, la mineralización fue significativamente acelerada, pero la resorción se mantuvo igual. Conclusiones: Este modelo sugiere que la PGE1 favorece la disyunción palatina y el aumento del calcitriol, y acelera la mineralización y el anabolismo óseo por modelación predominante sin hipercalcemia.

Histological comparison between biphasic calcium phosphate and deproteinized bovine bone on critical-size bone defects

Abstract The limited options for bone repair have led to an extensive research of the field and the development of alloplastic and xenogeneic grafts. The purpose of this study was to evaluate bone repair with two bone substitutes: deproteinized bovine bone (DBB) and biphasic calcium phosphate ceramic (BCP) in critical-size defect. A total of 8-mm defects were made in the parietal bones of rabbits (n=12). The animals were divided into three experimental groups: sham (defect filled with a blood clot), DBB (defect filled with DBB), and BCP (defect filled with BCP). After the experimental periods of 15 and 45 days, the animals were euthanized and submitted to histomorphometric analysis. The total defect area, mineralized tissue area, biomaterial area, and soft tissue area were evaluated. A greater amount of immature bone tissue and biomaterial particles were observed in the BCP group compared to DBB and sham at 45 days (p<0.05). There was no difference in the qualitative pattern of bone deposition between DBB and BCP. However, the sham group did not show osteoid islands along with the defect, presenting a greater amount of collagen fibers as well in relation to the DBB and BCP groups. There was a greater number of inflammatory cells in the DBB at 45 days compared to BCP and sham groups. In conclusion, BCP and DBB are options for optimizing the use of bone grafts for maxillofacial rehabilitation. Bone defects treated with BCP showed greater deposition of bone tissue at 45 days.

Resumo As opções limitadas para reparo ósseo levaram ao desenvolvimento de abrangente pesquisa na área de enxertos aloplásticos e xenogênicos. O objetivo deste estudo foi avaliar o reparo ósseo com dois substitutos ósseos: osso bovino desproteinizado (DBB) e cerâmica fosfática de cálcio bifásica (BCP) em defeito de tamanho crítico. Material e métodos: defeitos críticos de 8 mm foram feitos nos ossos parietais de coelhos (n=12). Os animais foram divididos em três grupos experimentais: sham (defeito preenchido com coágulo sanguíneo), DBB (defeito preenchido com DBB) e BCP (defeito preenchido com BCP). Após os períodos experimentais de 15 e 45 dias, os animais foram sacrificados e submetidos à análise histomorfométrica. Foram avaliadas a área total de defeitos, área de tecidos mineralizados, área de biomateriais e área de tecidos moles. Resultados: maior quantidade de tecido ósseo imaturo e de partículas de biomaterial foram observados no grupo BCP em comparação aos grupos DBB e sham aos 45 dias (p<0,05). Não houve diferença no padrão qualitativo de deposição óssea entre DBB e BCP. Ainda, o grupo sham não apresentou ilhas osteóides ao longo do defeito, apresentando maior quantidade de fibras colágenas em relação aos grupos DBB e BCP. Houve maior quantidade de células inflamatórias no DBB aos 45 dias em comparação aos grupos BCP e sham. Conclusões: BCP e DBB são opções para otimizar o uso de enxertos ósseos na reabilitação de pacientes. Defeitos ósseos tratados com BCP mostraram maior deposição de tecido ósseo aos 45 dias.

The Effect of Materials and Porosity on Bone Formation of Degradable Scaffolds / 医用生物力学

Objective To study the effect of different materials and porosities on bone formation in the scaffold after implantation of the degradable bone scaffold into human body. Methods According to natural reaction mechanism of fracture healing, the finite element method was used, combined with geometry of the scaffold, to establish a computationally coupled model based on material degradation curve and bone reconstruction control equation. Through this platform, representative volume elements of the scaffold with five kinds of materials and four types of porosities were selected for calculation and analysis, and dynamic process was reflected by bone mineral density (BMD) and maximum stress of the scaffold. Results The elastic modulus of the materials had a greater influence on growth of bone tissues in the scaffold. The smaller elastic modulus of the materials would lead to the greater amount of bone formation, but it would also have a greater impact on mechanical properties of the scaffold. The scaffold with higher porosity had lower rigidity, which could better promote formation of bone tissues, meanwhile it would also destroy mechanical stability of the scaffold. Conclusions According to performance requirements for different age, gender and location of bone tissues, personalized reference and calculation basis for selection of materials and porosity, structural design and clinical application of degradable porous bone scaffolds can be provided.

Signal Pathways Regulating Bone Formation / 中国生物化学与分子生物学报

Postnatal skeletal growth and bone remodeling are highly coordinated processes that are primarily mediated by bone formation and bone resorption. The imbalance in bone formation relative to bone resorption will result in the net bone loss that results in changes of bone microenvironment and increased fragility, leading to diseases such as osteoporosis and bone fracture. Bone formation is mediated by osteoblasts, which mainly derived from mesenchymal stem cells (MSCs). Bone formation process is regulated by multiple signal pathways. It has been found that Wnt/ β-catenin, BMP / Smads, MAPK and other pathways are involved in the regulation of osteoblast differentiation and bone formation. In addition, some signaling related molecules may also contribute to the number increase of osteoblasts and enhanced vascularization, such as growth factors FGF, PDGF, and VEGF. These factors have been regarded as targets to promote bone formation, therefore it is important to understand their underlying molecular mechanisms. This review summarizes the latest research progress on regulatory mechanisms and clinical translational application about the above pathways on promoting bone formation, mesenchymal stem cells growth and differentiation, aiming to provide theoretical basis and directions for searching new potential candidate drugs to promote bone formation.

Research progress of miRNAs in exosomes derived from bone-related cells regulating bone formation / 中国药理学通报

Exosome is a goblet-shaped extracellular vesicle with a lipid bilayer structure, and its diameter is about 30-150 nm. Exosomes participate in cell-to-cell communication by transporting proteins, miRNAs, and other biologically active factors, thereby affecting recipient cells. In recent years, a lot of studies have shown that exosomes derived from bone-related cells can not only mediate intercellular communication within the bone marrow microenvironment in a range of physiological conditions, but also contribute to the multiple pathological conditions in skeletal disorders. Here, we summarized the regulation of miR-NA in exosomes derived from bone-related cells on bone formation.

Bone turnover characteristics in patients with alcohol-induced osteonecrosis of the femoral head / 中国组织工程研究

BACKGROUND: The pathological changes of alcohol-induced osteonecrosis of the femoral head (ONFH) are the result of a combination of various factors, and its specific pathogenesis is inconclusive. Related studies have shown abnormal bone metabolism in patients with avascular necrosis of the femoral head. OBJECTIVE: To explore the bone turnover markers in patients with alcohol-induced ONFH and to explore the relationship between different stages of ONFH and bone metabolism. METHODS: This study retrospectively selected 193 male patients with alcohol-induced ONFH (necrosis group), including 35 cases of ARCO stage II, 131 cases of ARCO stage III and 27 cases of ARCO stage IV. Among them, there were 65 cases of a little drinking of alcohol 52 cases of moderate drinking, and 76 cases of heavy drinking. Another 182 healthy males undergoing physical examination with no history of drinking were taken as control group. The bone turnover markers [procollagen type 1 N-terminal propeptide (P1NP), C-terminal cross-linked telopeptides of type 1 collagen (β-CTX), molecular fragment of N-terminal osteocalcin (N-MID) and 25 hydroxyvitamin D (25OHD)] and biochemical indexes were tested and compared between two groups, followed by logistic regression analysis and correlation analysis. The study protocol was performed in line with the relevant ethic requirements of the First Affiliated Hospital of Guangzhou University of Chinese Medicine. All participants in the trial had been fully informed of the trial process. RESULTS AND CONCLUSION: In the necrosis group, P1NP, β-CTX, N-MID, 25OHD, serum calcium, uric acid, alkaline phosphatase, serum phosphorus levels were significantly higher than that of the control group (P < 0.05), and apolipoprotein A1 and high-density lipoprotein levels in the necrosis group were significantly lower than those in the control group (P < 0.05). Compared with patients with low level of alcohol, β-CTX and N-MID levels were significantly reduced in the patients with heavy drinking (P < 0.05). The P1NP level of patients with ARCO stage IV was significantly higher than that of patients with ARCO stage II and III (P < 0.05), and the β-CTX level of patients with ARCO stage IV was significantly higher than that of patients with ARCO stage III (P < 0.05). The correlation analysis results showed that alcohol intake levels were negatively correlated with β-CTX, alkaline phosphatase level was positively correlated with P1NP and β-CTX, and 25OHD was negatively correlated with low-density lipoprotein. Logistic regression analysis results showed that: P1NP (odds ratio=0.984, P=0.004), β-CTX (odds ratio=0.325, P=0.043), and high-density lipoprotein (odds ratio=2.622, P=0.014). To conclude, male patients with alcohol-induced ONFH have active bone formation and bone resorption, and obvious abnormalities in lipid metabolism. The progression of alcohol-induced ONFH can be predicted by these bone turnover markers.

Research status of 3D⁃printed composite PVA bone tissue engineering scaffolds / 口腔疾病防治

@# Three dimensionally printed composite porous bone tissue engineering scaffolds have become a research focus. Composite polyvinyl alcohol (PVA) has good biocompatibilityand degradability, but it cannot be prepared indepen⁃dently because it cannot resist highmechanical resistance. This material shows many advantages, such as good biocom⁃patibility, degradability and mechanical properties, when compounded with other materials with good mechanical proper⁃ties and good biocompatibility. Therefore, 3D printed composite PVA scaffold material can optimize the performance of PVA scaffolds. This article reviews 3D printing bone scaffold technology, polyvinyl alcohol (PVA), and composite PVA scaffolds for in vivo and in vitro bone formation.

Corylin inhibits osteoclastogenesis and attenuates postmenopausal osteoporosis in mice / 中国组织工程研究

BACKGROUND: The balance of bone homeostasis is mediated by the osteoclast-related bone resorption and osteoblast-related bone formation. Over-activation of osteoclasts results in a series of bone metabolic diseases including rheumatoid arthritis and osteoporosis. The activation of nuclear factor-κB pathway induced by receptor activator of nuclear factor-κB ligand (RANKL) plays an important role in osteoclastogenesis. OBJECTIVE: To explore the effect of corylin on RANKL-mediated osteoclastogenesis. METHODS: RAW264.7 cells were incubated with 0, 1, 2, 4, 8, 16, 32, 64, 128 μmol/L corylin. The cytotoxicity of corylin was detected by cell counting kit-8 assay. RANKL induced the differentiation of RAW264.7 cells into osteoclasts, during which 2, 5, 10 μmol/L corylin was given. The number of osteoclasts was analyzed by TRAP staining after 5 days of intervention and the morphology and function of osteoclasts were analyzed by F-actin staining. Bone resorption assay was conducted after 2 days of intervention. The activation of nuclear factor-κB pathway was detected by western blot at 0, 15, 30, and 60 minutes of intervention. Then in vivo experiments were carried out, and the ovariectomized mice were intraperitoneally given 10 mg/kg twice a week. After 6 weeks of intervention, mouse femurs were taken for morphological analysis. RESULTS AND CONCLUSION: There was no cytotoxicity of corylin below the concentration of 16 μmol/L. Corylin inhibited osteoclastogenesis in a dose-dependent manner. Corylin inhibited the formation of F-actin and resorption activity of osteoclasts. Corylin inhibited RANKL-mediated nuclear factor-κB pathway. Corylin treatment reduced the bone loss in postmenopausal osteoporosis mice. Overall, corylin inhibits osteoclastogenesis via blocking nuclear factor-κB pathway and attenuates postmenopausal osteoporosis.

Mechanism of action of energy metabolism molecule sirt1 in improving bone metabolism of type 2 diabetes / 中国组织工程研究

BACKGROUND: Energy metabolism regulates type 2 diabetes bone metabolism is a hotspot in the field of life medicine. Long-term disorders of energy metabolism such as sugar and lipids lead to insulin resistance, which triggers type 2 diabetes. Silent information regulator 1 (SIRT1), a nicotinamide adenine dinucleotide- dependent histone deacetylase, is a key factor regulating energy metabolism and is involved in bone metabolism, gene transcription, cellular senescence, apoptosis and pyroptosis. OBJECTIVE: To analyze the recent literature on the mechanism of action of SIRT1 in exercise-improving bone metabolism, and to investigate its current status and research progress. METHODS: Databases of PubMed and CNKI were retrieved. The keywords were “SIRT1, exercise, type 2 diabetes, bone formation, bone resorption” in Chinese and English, respectively. RESULTS AND CONCLUSION: (1) The differentiation and function of osteoblasts and osteoclasts and the metabolic balance are the key to ensure the homeostasis of bone metabolism. In the event of a disorder, the morphological structure of the bone tissue will be degraded, which is also an important mechanism for the occurrence of osteoporosis in type 2 diabetes complications. (2) Energy metabolism disorder is critical for triggering type 2 diabetes. SIRT1, as a key factor regulating energy metabolism, can mediate osteoblast and osteoclast differentiation and function through Wnt and transforming growth factor-)} pathways. (3) Recently, exercise has been shown to significantly improve the energy metabolism and bone metabolism of type 2 diabetes. Based on the osteoblasts and osteoclasts, the current researches at home and abroad are reviewed to explore the mechanism of SIRT1 in the improvement of type 2 diabetes bone metabolism.