Crosstalk between Wnt and bone morphogenetic protein signaling during osteogenic differentiati

Mesenchymal stem cells(MSCs)originate from many sources,including the bone marrow and adipose tissue,and differentiate into various cell types,such as osteoblasts and adipocytes.Recent studies on MSCs have revealed that many transcription factors and signaling pathways control osteogenic development.Osteogenesis is the process by which new bones are formed;it also aids in bone remodeling.Wnt/β-catenin and bone morphogenetic protein(BMP)signaling pathways are involved in many cellular processes and considered to be essential for life.Wnt/β-catenin and BMPs are important for bone formation in mammalian development and various regulatory activities in the body.Recent studies have indicated that these two signaling pathways contribute to osteogenic differen-tiation.Active Wnt signaling pathway promotes osteogenesis by activating the downstream targets of the BMP signaling pathway.Here,we briefly review the molecular processes underlying the crosstalk between these two pathways and explain their participation in osteogenic differentiation,emphasizing the canonical pathways.This review also discusses the crosstalk mechanisms of Wnt/BMP signaling with Notch-and extracellular-regulated kinases in osteogenic differentiation and bone development.

The marriage of immunomodulatory,angiogenic,and osteogenic capabilities in a piezoelectric hydrogel tissue engineering scafold for military medicine

Background:Most bone-related injuries to grassroots troops are caused by training or accidental injuries.To establish preventive measures to reduce all kinds of trauma and improve the combat effectiveness of grassroots troops,it is imperative to develop new strategies and scafolds to promote bone regeneration.Methods:In this study,a porous piezoelectric hydrogel bone scafold was fabricated by incorporating polydopamine(PDA)-modified ceramic hydroxyapatite(PDA-hydroxyapatite,PHA)and PDA-modified barium titanate(PDABaTiO_(3),PBT)nanoparticles into a chitosan/gelatin(Cs/Gel)matrix.The physical and chemical properties of the Cs/Gel/PHA scafold with 0–10 wt%PBT were analyzed.Cell and animal experiments were performed to characterize the immunomodulatory,angiogenic,and osteogenic capabilities of the piezoelectric hydrogel scafold in vitro and in vivo.Results:The incorporation of BaTiO_(3) into the scafold improved its mechanical properties and increased self-generated electricity.Due to their endogenous piezoelectric stimulation and bioactive constituents,the prepared Cs/Gel/PHA/PBT hydrogels exhibited cytocompatibility as well as immunomodulatory,angiogenic,and osteogenic capabilities;they not only effectively induced macrophage polarization to M2 phenotype but also promoted the migration,tube formation,and angiogenic differentiation of human umbilical vein endothelial cells(HUVECs)and facilitated the migration,osteodifferentiation,and extracellular matrix(ECM)mineralization of MC3T3-E1 cells.The in vivo evaluations showed that these piezoelectric hydrogels with versatile capabilities significantly facilitated new bone formation in a rat large-sized cranial injury model.The underlying molecular mechanism can be partly attributed to the immunomodulation of the Cs/Gel/PHA/PBT hydrogels as shown via transcriptome sequencing analysis,and the PI3K/Akt signaling axis plays an important role in regulating macrophage M2 polarization.Conclusion:The piezoelectric Cs/Gel/PHA/PBT hydrogels developed here with favorable immunomodulation,angiogenesis,and osteogenesis functions may be used as a substitute in periosteum injuries,thereby offering the novel strategy of applying piezoelectric stimulation in bone tissue engineering for the enhancement of combat efectiveness in grassroots troops.

O-linkedβ-N-acetylglucosaminylation may be a key regulatory factor in promoting osteogenic differentiation of bone marrow mesenchymal stromal cells

Cumulative evidence suggests that O-linkedβ-N-acetylglucosaminylation(OGlcNAcylation)plays an important regulatory role in pathophysiological processes.Although the regulatory mechanisms of O-GlcNAcylation in tumors have been gradually elucidated,the potential mechanisms of O-GlcNAcylation in bone metabolism,particularly,in the osteogenic differentiation of bone marrow mesenchymal stromal cells(BMSCs)remains unexplored.In this study,the literature related to O-GlcNAcylation and BMSC osteogenic differentiation was reviewed,assuming that it could trigger more scholars to focus on research related to OGlcNAcylation and bone metabolism and provide insights into the development of novel therapeutic targets for bone metabolism disorders such as osteoporosis.

Solitary Osteogenic Exostosis of the Femur Revealed by Recurring Acute Distal Thigh Pain: About a Case

Introduction: Solitary exostoses are the most common benign tumors of the fertile metaphyses of the long bones of children. Their radiological diagnosis of metaphyseal bone growth must be confirmed on pathological examination. These tumors can remain asymptomatic for a long time and reveal themselves during a particularly vascular complication. The objective of this study was to describe the epidemiological, diagnostic, therapeutic and evolutionary aspects of these tumors. Patient and Observation: We report the case of a 15-year-old adolescent girl, with no particular pathological history, received in the pediatric surgery department of the Donka National Hospital (HND) of the Conakry University Hospital for recurrent acute painful swelling of the lower third of the left thigh in an afebrile context accompanied by lameness and stopping school for a few days (2 - 3 days). The symptoms appear to have evolved over the past 3 years and after physical activities. It regresses with rest, analgesics and non-steroidal anti-inflammatory drugs. The notion of trauma and sickle cell disease was not reported in the patient's clinical history. It is the persistence of the symptomatology which motivates the said consultation. On palpation, a small hard mass is noted at the expense of the internal metaphysis of the left distal femur. Deep palpation of this area causes a tingling sensation and during rapid mobilization of the knee. The remainder of the orthopedic examination was unremarkable. Standard x-ray of the femur shows a bony growth with a pointed tip from the distal metaphysis of the left femur. On surgical exploration, we noted a wedge-shaped exostosis oriented towards the vastus medialis muscle. Histological examination of the surgical specimen confirms osteogenic exostosis. There is no recurrence after 2 years. Conclusion: The distal femoral metaphysis is the most common location of solitary osteochondromas in children. Their definitive diagnosis requires the histology of the surgical specimen. Only symptomatic exostoses should be operated on in children.

RPLP0/TBP are the most stable reference genes for human dental pulp stem cells under osteogenic differentiation

BACKGROUND Validation of the reference gene(RG)stability during experimental analyses is essential for correct quantitative real-time polymerase chain reaction(RT-qPCR)data normalisation.Commonly,in an unreliable way,several studies use genes involved in essential cellular functions[glyceraldehyde-3-phosphate dehydro-genase(GAPDH),18S rRNA,andβ-actin]without paying attention to whether they are suitable for such experimental conditions or the reason for choosing such genes.Furthermore,such studies use only one gene when Minimum Information for Publication of Quantitative Real-Time PCR Experiments guidelines recom-mend two or more genes.It impacts the credibility of these studies and causes dis-tortions in the gene expression findings.For tissue engineering,the accuracy of gene expression drives the best experimental or therapeutical approaches.We cultivated DPSCs under two conditions:Undifferentiated and osteogenic dif-ferentiation,both for 35 d.We evaluated the gene expression of 10 candidates for RGs[ribosomal protein,large,P0(RPLP0),TATA-binding protein(TBP),GAPDH,actin beta(ACTB),tubulin(TUB),aminolevulinic acid synthase 1(ALAS1),tyro-sine 3-monooxygenase/tryptophan 5-monooxygenase activation protein,zeta(YWHAZ),eukaryotic translational elongation factor 1 alpha(EF1a),succinate dehydrogenase complex,subunit A,flavoprotein(SDHA),and beta-2-micro-globulin(B2M)]every 7 d(1,7,14,21,28,and 35 d)by RT-qPCR.The data were analysed by the four main algorithms,ΔCt method,geNorm,NormFinder,and BestKeeper and ranked by the RefFinder method.We subdivided the samples into eight subgroups.RESULTS All of the data sets from clonogenic and osteogenic samples were analysed using the RefFinder algorithm.The final ranking showed RPLP0/TBP as the two most stable RGs and TUB/B2M as the two least stable RGs.Either theΔCt method or NormFinder analysis showed TBP/RPLP0 as the two most stable genes.However,geNorm analysis showed RPLP0/EF1αin the first place.These algorithms’two least stable RGs were B2M/GAPDH.For BestKeeper,ALAS1 was ranked as the most stable RG,and SDHA as the least stable RG.The pair RPLP0/TBP was detected in most subgroups as the most stable RGs,following the RefFinfer ranking.CONCLUSION For the first time,we show that RPLP0/TBP are the most stable RGs,whereas TUB/B2M are unstable RGs for long-term osteogenic differentiation of human DPSCs in traditional monolayers.

Exercise promotes osteogenic differentiation by activating the long non-coding RNA H19/microRNA-149 axis

BACKGROUND Regular physical activity during childhood and adolescence is beneficial to bone development,as evidenced by the ability to increase bone density and peak bone mass by promoting bone formation.AIM To investigate the effects of exercise on bone formation in growing mice and to investigate the underlying mechanisms.METHODS 20 growing mice were randomly divided into two groups:Con group(control group,n=10)and Ex group(treadmill exercise group,n=10).Hematoxylin-eosin staining,immunohistochemistry,and micro-CT scanning were used to assess the bone formation-related indexes of the mouse femur.Bioinformatics analysis was used to find potential miRNAs targets of long non-coding RNA H19(lncRNA H19).RT-qPCR and Western Blot were used to confirm potential miRNA target genes of lncRNA H19 and the role of lncRNA H19 in promoting osteogenic differentiation.RESULTS Compared with the Con group,the expression of bone morphogenetic protein 2 was also significantly increased.The micro-CT results showed that 8 wk moderate-intensity treadmill exercise significantly increased bone mineral density,bone volume fraction,and the number of trabeculae,and decreased trabecular segregation in the femur of mice.Inhibition of lncRNA H19 significantly upregulated the expression of miR-149 and suppressed the expression of markers of osteogenic differentiation.In addition,knockdown of lncRNA H19 significantly downregulated the expression of autophagy markers,which is consistent with the results of autophagy-related protein changes detected in mouse femurs by immunofluorescence.CONCLUSION Appropriate treadmill exercise can effectively stimulate bone formation and promote the increase of bone density and bone volume in growing mice,thus enhancing the peak bone mass of mice.The lncRNA H19/miR-149 axis plays an important regulatory role in osteogenic differentiation.

Adipokines regulate mesenchymal stem cell osteogenic differentiation

Mesenchymal stem cells(MSCs)can differentiate into various tissue cell types including bone,adipose,cartilage,and muscle.Among those,osteogenic differentiation of MSCs has been widely explored in many bone tissue engineering studies.Moreover,the conditions and methods of inducing osteogenic differentiation of MSCs are continuously advancing.Recently,with the gra-dual recognition of adipokines,the research on their involvement in different pathophysiological processes of the body is also deepening including lipid metabolism,inflammation,immune regulation,energy disorders,and bone homeostasis.At the same time,the role of adipokines in the osteogenic differentiation of MSCs has been gradually described more completely.Therefore,this paper reviewed the evidence of the role of adipokines in the osteogenic differentiation of MSCs,emphasizing bone formation and bone regeneration.

Stimulating factors for regulation of osteogenic and chondrogenic differentiation of mesenchymal stem cells

Mesenchymal stem cells(MSCs),distributed in many tissues in the human body,are multipotent cells capable of differentiating in specific directions.It is usually considered that the differentiation process of MSCs depends on specialized external stimulating factors,including cell signaling pathways,cytokines,and other physical stimuli.Recent findings have revealed other underrated roles in the differentiation process of MSCs,such as material morphology and exosomes.Although relevant achievements have substantially advanced the applicability of MSCs,some of these regulatory mechanisms still need to be better understood.Moreover,limitations such as long-term survival in vivo hinder the clinical application of MSCs therapy.This review article summarizes current knowledge regarding the differentiation patterns of MSCs under specific stimulating factors.

A novel mutation in ROR2 led to the loss of function of ROR2 and inhibited the osteogenic differentiation capability of bone marrow mesenchymal stem cells(BMSCs)

Receptor tyrosine kinase-like orphan receptor 2(ROR2)has a vital role in osteogenesis.However,the mechanism underlying the regulation of ROR2 in osteogenic differentiation is still poorly comprehended.A previous study by our research group showed that a novel compound heterozygous ROR2 variation accounted for the autosomal recessive Robinow syndrome(ARRS).This study attempted to explore the impact of the ROR2:c.904C>T variant specifically on the osteogenic differentiation of BMSCs.Methods:Coimmunoprecipitation(CoIP)-western blotting was carried out to identify the interaction between ROR2 and Wnt5a.Double-immunofluorescence staining was used for determining the expressions and co-localization of ROR2 and Wnt5a in bone marrow mesenchymal stem cells(BMSCs).Western blot(WB)analysis and quantitative reverse transcription polymerase chain reaction(RT-qPCR)were conducted to identify the expression levels of ROR2 in the BMSCs transfected with LV-shROR2 or LV-ROR2-c.904C>T.The alkaline phosphatase(ALP)activity was detected,and Alizarin Red S staining was done for evaluating the osteogenic differentiation of BMSCs.RT-qPCR was employed to identify the expression of the sphingomyelin synthase 1(SMS1)mRNA in the BMSCs transfected with LV-shROR2 or LV-ROR2-c.904C>T and the mRNA expression levels of Runt-related transcription factor 2(RUNX2),osteocalcin(OCN),and osteopontin(OPN).WB was performed to confirm the protein expressions of extracellular regulated protein kinases1(ERK),P-ERK,Smad family member1/5/8(Smad1/5/8),P-Smad1/5/8,P-P38,P38,RUNX2,OCN,and OPN in the BMSCs transfected with LV-shROR2/LV-ROR2-c.904C>T and sphingomyelin(SM).Results:The ROR2:c.904C>T mutant altered the subcellular localization of the ROR2 protein,which caused an impaired interaction between ROR2 and Wnt5a.The depletion of ROR2 restricted the osteogenic differentiation capability of BMSCs and downregulated the expression of SMS1.SM treatment could reverse the inhibition of osteoblastic differentiation in ROR2-depleted BMSCs.Conclusion:The findings of this work revealed that the ROR2:c.904C>T variant led to the loss of function of ROR2,which impaired the interaction between ROR2 and Wnt5a and also controlled the osteogenic differentiation capability of BMSCs.Furthermore,SM was revealed to be engaged in the osteoblastic differentiation of BMSCs regulated by ROR2,which renders SM a potential target in the therapy for ARRS.

MicroRNA-584-5p/RUNX family transcription factor 2 axis mediates hypoxia-induced osteogenic differentiation of periosteal stem cells

BACKGROUND The hypoxic environment during bone healing is important in regulating the differentiation of periosteal stem cells(PSCs)into osteoblasts or chondrocytes;however,the underlying mechanisms remain unclear.AIM To determine the effect of hypoxia on PSCs,and the expression of microRNA-584-5p(miR-584-5p)and RUNX family transcription factor 2(RUNX2)in PSCs was modulated to explore the impact of the miR-584-5p/RUNX2 axis on hypoxiainduced osteogenic differentiation of PSCs.METHODS In this study,we isolated primary mouse PSCs and stimulated them with hypoxia,and the characteristics and functional genes related to PSC osteogenic differentiation were assessed.Constructs expressing miR-584-5p and RUNX2 were established to determine PSC osteogenic differentiation.RESULTS Hypoxic stimulation induced PSC osteogenic differentiation and significantly increased calcified nodules,intracellular calcium ion levels,and alkaline phosphatase(ALP)activity in PSCs.Osteogenic differentiation-related factors such as RUNX2,bone morphogenetic protein 2,hypoxia-inducible factor 1-alpha,and ALP were upregulated;in contrast,miR-584-5p was downregulated in these cells.Furthermore,upregulation of miR-584-5p significantly inhibited RUNX2 expression and hypoxia-induced PSC osteogenic differentiation.RUNX2 was the target gene of miR-584-5p,antagonizing miR-584-5p inhibition in hypoxia-induced PSC osteogenic differentiation.CONCLUSION Our study showed that the interaction of miR-584-5p and RUNX2 could mediate PSC osteogenic differentiation induced by hypoxia.

Exploring the Mechanism of CircRNA-vgll3 in Osteogenically Differentiated Human Bone Marrow Mesenchymal Stem Cells

Objective:To explore the mechanism of circRNA-vgll3 in osteogenic differentiation of human bone marrow mesenchymal stem cells.Methods:BMSCs cells were transfected with circRNA-vgll3,and divided into circRNA-vgll3 high-level group,circRNA-vgll3 low-level group,and negative control group(circRNA-vgll3 not transfected)according to the amount of transfection.The proliferation and apoptosis of BMSCs osteoblasts in each group were analyzed,and the alkaline phosphatase(ALP)activity,type I collagen gray value,bone morphogenetic protein 2(BMP-2),Runx2 protein,and mRNA expression levels were detected.Results:The circRNA-vgll3 low-level group had a significant inhibitory effect on the proliferation of BMSCs osteoblasts,and the apoptosis rate of the circRNA-vgll3 low-level group was significantly higher than that of the circRNA-vgll3 high-level group(P<0.05);ALP activity,type I collagen gray value,BMP-2,Runx2 protein,and mRNA expression levels in the high-level circRNA-vgll3 group were significantly higher than those in the low-level circRNA-vgll3 group,and the difference was statistically significant(P<0.05).Conclusion:Overexpression of circRNA-vgll3 can promote the osteogenic differentiation ability of BMSCs,while low expression of circRNA-vgll3 can inhibit the osteogenic differentiation ability of BMSCs.The main mechanism of action is that circRNA-vgll3 can affect osteogenic differentiation by regulating the Runx2 protein.

Supportive angiogenic and osteogenic differentiation of mesenchymal stromal cells and endothelial cells in monolayer and co-cultures

Sites of implantation with compromised biology may be unable to achieve the required level of angiogenic and osteogenic regeneration. The specific function and contribution of different cell types to the formation of prevascularized, osteogenic networks in co-culture remains unclear. To determine how bone marrow-derived mesenchymal stromal cells （BMSCs） and endothelial cells （ECs） contribute to cellular proangiogenic differentiation, we analysed the differentiation of BMSCs and ECs in standardized monolayer, Transwell and co-cultures. BMSCs were derived from the iliac bone marrow of five patients, characterized and differentiated in standardized monolayers, permeable Transwells and co-cultures with human umbilical vein ECs （HUVECs）. The expression levels of CD31, von Willebrand factor, osteonectin （ON） and Runx2 were assessed by quantitative reverse transcriptase polymerase chain reaction. The protein expression of alkaline phosphatase, ON and CD31 was demonstrated via histochemical and immunofluorescence analysis. The results showed that BMSCs and HUVECs were able to retain their lineage-specific osteogenic and angiogenic differentiation in direct and indirect co-cultures. In addition, BMSCs demonstrated a supportive expression of angiogenic function in co-culture, while HUVEC was able to improve the expression of osteogenic marker molecules in BMSCs.

Osteogenic Effect of Low Intensity Pulsed Ultrasound on Rat Adipose-derived Stem Cells in vitro

The osteogenic in vitro effect of low intensity pulsed ultrasound (LIPUS) on SD rat adi-pose-derived stem cells (ADSCs) was investigated.Rat ADSCs underwent LIPUS (intensity=100 mW/cm2) or sham exposure for 8 min per treatment once everyday in vitro,and then the alkaline phos-phatase (ALP) activity and mineralized nodule formation were assessed to evaluate the osteogenic effect of LIPUS on ADSCs.To further explore the underlying mechanism,the osteogenic-related gene mRNA expression was determined by using reverse transcriptase-polymerase chain reaction (RT-PCR) at 1st,3rd,5th,7th day after exposure repectively.Westen blot was used to evaluate the protein expression levels of two osteogenic differentiation associated genes at 7th and 14th day repectively.It was found that ALP activity was increased after LIPUS exposure and LIPUS resulted in mineralized nodule formation of ADSCs in vitro.LIPUS-treated ADSCs displayed higher mRNA expression levels of runt-related transcription factor 2 (Runx2),osteocalcin (OCN),ALP and bone sialoprotein (BSP) genes than con-trols,and the protein levels of Runx2 and BSP were also increased.The results suggested that LIPUS may induce the osteogenic differentiation of ADSCs in vitro.

Low-power laser irradiation promotes the proliferation and osteogenic differentiation of human periodontal ligament cells via cyclic adenosine monophosphate

Retaining or improving periodontal ligament （PDL） function is crucial for restoring periodontal defects. The aim of this study was to evaluate the physiological effects of low-power laser irradiation （LPLI） on the proliferation and osteogenic differentiation of human PDL （hPDL） cells. Cultured hPDL cel Is were irradiated （660 nm） daily with doses of O, 1, 2 or 4 J .cm-2. Cell proliferation was evaluated by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide （MTT） assay, and the effect of LPLI on osteogenic differentiation was assessed by Alizarin Red S staining and alkaline phosphatase （ALP） activity. Additionally, osteogenic marker gene expression was confirmed by real-time reverse transcription-polymerase chain reaction （RT-PCR）. Our data showed that LPLI at a dose of 2 J.cm-2 significantly promoted hPDL cell proliferation at days 3 and 5. In addition, LPLI at energy doses of 2 and 4 J.cm-2 showed potential osteogenic capacity, as it stimulated ALP activity, calcium deposition, and osteogenic gene expression. We also showed that cyclic adenosine monophosphate （cAMP） is a critical regulator of the LPLI-mediated effects on hPDL cells. This study shows that LPLI can promote the proliferation and osteogenic differentiation of hPDL cells. These results suggest the potential use of LPLI in clinical applications for periodontal tissue regeneration.

Effect of rhBMP-2 and Osteogenic Revulsants on Proliferation and Differentiation of Bone Marrow Stromal Cells in Rats

The effects of recombinant human bone morphogenetic protein-2 （rhBMP-2） and osteogenic revulsants alone or in combination at different time points and in different dosages on proliferation and osteogenesis of bone marrow stromal cells （BMSCs） in SD rats were investigated. Rat BMSCs were cultured in vitro and induced by rhBMP-2 in different dosages （10, 50, 100 and 200μg/L） alone or in combination with osteogenic revulsants. MTT colorimetric assay was used to evaluate The proliferation, activity of alkaline phosphoric （ALP） and osteocalcin were measured at 3rd, 6th, 9th, 12th day respectively. The results showed that rhBMP-2 and osteogenic revulsants could promote the differentiation of BMSCs towards osteoblast phenotype. The proliferation of BMSCs could be enhanced by rhBMP-2 in a dose-dependent manner. The expression of osteoblast phenotype was significantly higher by using both of them than by using them alone, which was verified by the activity of ALP and osteocalcin. It was suggested that the combined use of rhBMP-2 and osteogenic revulsants could promote the proliferation and simultaneously induce and maintain the expression of osteoblast phenotype of BMSCs in rats.

Overview of noncoding RNAs involved in the osteogenic differentiation of periodontal ligament stem cells

Periodontal diseases are infectious diseases that are characterized by progressive damage to dental support tissue.The major goal of periodontal therapy is to regenerate the periodontium destroyed by periodontal diseases.Human periodontal ligament(PDL)tissue possesses periodontal regenerative properties,and periodontal ligament stem cells(PDLSCs)with the capacity for osteogenic differentiation show strong potential in clinical application for periodontium repair and regeneration.Noncoding RNAs(ncRNAs),which include a substantial portion of poly-A tail mature RNAs,are considered“transcriptional noise.”Recent studies show that ncRNAs play a major role in PDLSC differentiation;therefore,exploring how ncRNAs participate in the osteogenic differentiation of PDLSCs may help to elucidate the underlying mechanism of the osteogenic differentiation of PDLSCs and further shed light on the potential of stem cell transplantation for periodontium regeneration.In this review paper,we discuss the history of PDLSC research and highlight the regulatory mechanism of ncRNAs in the osteogenic differentiation of PDLSCs.

Evaluation on the corrosion resistance, antibacterial property and osteogenic activity of biodegradable Mg-Ca and Mg-Ca-Zn-Ag alloys

The rapid degradation of magnesium(Mg)-based implants in physiological environment limits its clinical applications, and alloying treatment is an effective way to regulate the degradation rate of Mg-based materials. In the present study, three Mg alloys, including Mg-0.8Ca(denoted as ZQ), Mg-0.8Ca-5Zn-1.5Ag(denoted as ZQ71) and Mg-0.8Ca-5Zn-2.5Ag(denoted as ZQ63), were fabricated by alloying with calcium(Ca), zinc(Zn) and silver(Ag). The results obtained from electrochemical corrosion tests and in vitro degradation evaluation demonstrated that the three Mg alloys exhibited distinct corrosion resistance, and ZQ71 exhibited the lowest degradation rate in vitro among them. After addition of Zn and Ag, the antibacterial potential of Mg alloys was also enhanced. The in vitro cell experiments showed that all the three Mg alloys had good biocompatibility. After implantation in a rat femoral defect, ZQ71 showed significantly higher osteogenic activity and bone substitution rate than ZQ63 and ZQ, due to its higher corrosion resistance as well as the stimulatory effects of the released metallic ions. In addition, the average daily degradation rate of each Mg alloy in vivo was significantly higher than that in vitro, as could be due to the implantation site located in the highly vascularized trabecular region. Importantly, the correlations between the in vitro and in vivo degradation parameters of the Mg alloys were systematically analyzed to find out the potential predictors of the in vivo degradation performance of the materials. The current work not only evaluated the clinical potential of the three biodegradable Mg alloys as bone grafts but also provided a feasible approach for predicting the in vivo degradation behavior of biodegradable materials.

The Content of Silver, Cobalt, Chromium, Iron, Mercury, Rubidium, Antimony, Selenium, and Zinc in Osteogenic Sarcoma

Objectives: To clarify the role of trace elements in the etiology and the pathogenesis of the osteogenic sarcoma (osteosarcoma), a non-destructive neutron activation analysis with high resolution spectrometry of long-lived radionuclides was performed. Methods: The silver (Ag), cobalt (Co), chromium (Cr), iron (Fe), mercury (Hg), rubidium (Rb), antimony (Sb), selenium (Se), and zinc (Zn) mass fraction, Rb/Co, Rb/Fe, Rb/Se, and Rb/Zn mass fraction ratios as well as Co × Zn, Fe × Zn, Sb × Zn, Se × Zn, Co × Se, and Fe × Se mass fraction multiplications were estimated in normal bone samples from 27 patients with intact bone (12 females and 15 males, aged from 16 to 49 years), who had died from various non bone related causes, mainly unexpected from trauma, and in tumor samples, obtained from open biopsies or after operation of 27 patients with osteosarcoma (9 females and 18 males, 6 to 71 years old). The reliability of difference in the results between intact bone and osteosarcoma tissues was evaluated by Student’s t-test. Results: In the osteosarcoma tissue the mass fractions of Co, Cr, Fe, Sb, Se, and Zn are significantly higher while the mass fraction of Rb is lower than in normal bone tissues. Moreover, we found significantly lower values of Rb/Co, Rb/Fe, Rb/Se, and Rb/Zn mass fraction ratios as well as significant higher mean values of Co × Zn, Fe × Zn, Sb × Zn, Se × Zn, Co × Se, and Fe × Se mass fractions multiplications in the osteosarcoma tissue compared to intact bone. In the osteosarcoma tissue many correlations between trace elements found in the control group were no longer evident. Conclusion: In osteosarcoma transformed bone tissues the trace element homeostasis is significantly disturbed.

Periodontally accelerated osteogenic orthodontics with platelet-rich fibrin in an adult patient with periodontal disease:A case report and review of literature

BACKGROUND In the clinical scenario,adult patients with periodontal diseases and dental malformation,characterized by dental crowding in lower anterior teeth with the thin biotype,often require orthodontic treatment.This case report aimed to evaluate the clinical and radiographic outcomes of periodontally accelerated osteogenic orthodontics(PAOO)combined with autologous platelet-rich fibrin(PRF)in an adult patient with class I malocclusion along with dental crowding,a thin periodontal biotype,and buccal plate deficiency.CASE SUMMARY A 32-year-old female complaining of dental crowding and gingival bleeding was referred to the orthodontic clinic.The patient underwent periodontal risk assessment prior to orthodontic treatment.She was diagnosed with a high risk of gingival recession due to dental crowding,root prominence,loss of buccal plates,and a thin gingival tissue biotype.The treatment regimen included PAOO combined with autologous PRF for alveolar augmentation and interproximal enamel reduction for moderate dental crowding.Clinically,PAOO-assisted orthodontic tooth movement in this case showed enhanced periodontium remodeling.Radiographic outcomes also showed statistically significant improvements(P<0.01)in the mandibular buccal alveolar bone.CONCLUSION This case report suggests the combination of autologous PRF with PAOO to enhance bone augmentation and long-term tissue support in adult orthodontic patients with periodontal disease.

TGF-beta 1 Gene-Activated Matrices Regulated the Osteogenic Differentiation of BMSCs

Poly （lactic acid/glycolic acid/asparagic acid-co-polyethylene glycol）（PLGA-[ASP-PEG]） scaffold materials were linked with a novel nonviral vector （K）16GRGDSPC through cross linker Sulfo- LC-SPDP to construct a new type of nonviral gene transfer system. Eukaryotic expressing vector containing transforming growth factor beta 1 （pcDNA3-TGFβ1） was encapsulated by the system. Bone marrow stromal cells （BMSCs） obtained from rabbit were cultured on PLGA-[ASP-PEG] modified by （K）16GRGDSPC and TGF-β1 gene and PLGA-[ASP-PEG] modified by （K）16GRGDSPC and empty vector pcDNA3 as control. The expressions of osteogenic makers of the BMSCs cultured on the TGF-β1 gene-activated scaffold materials were found significantly higher than those of the control group （P〈0.05）. A brand-new way was provided for regulating seed cells to directionally differentiate into osteoblasts for bone defect restoration in bone tissue engineering.