Can zoledronic acid reduce the risk of cage subsidence after oblique lumbar interbody fusion combined with bilateral pedicle screw fixation in the elderly population? A retrospective study.

BACKGROUND: The objective of this study was to evaluate the potential of zoledronic acid for reducing the incidence of cage subsidence and enhancing interbody fusion rates following oblique lumbar interbody fusion (OLIF) surgery, particularly as the first reported evidence of the role of zoledronic acid combined with OLIF. METHODS: A retrospective analysis was conducted on data from 108 elderly patients treated for degenerative lumbar diseases using OLIF combined with bilateral pedicle screw fixation from January 2018 to December 2021. Patients were divided into the zoledronic acid (ZOL) group (43 patients, 67 surgical segments) and the control group (65 patients, 86 surgical segments). A comparative analysis of the radiographic and clinical outcomes between the groups was performed, employing univariate and multivariate regression analyses to explore the relationships between cage subsidence and the independent variables. RESULTS: Radiographic outcomes, including anterior height, posterior height, disc height, coronal disc angle, foraminal height, and lumbar lordosis, were not significantly different between the two groups. Similarly, no statistically significant differences were noted in the back visual analog scale (VAS) scores and Oswestry Disability Index (ODI) scores between the groups. However, at the 1-year follow-up, the leg VAS score was lower in the ZOL group than in the control group (P = 0.028). The ZOL group demonstrated a notably lower cage subsidence rate (20.9%) than did the control group (43.0%) (P < 0.001). There was no significant difference in the interbody fusion rate between the ZOL group (93.0%) and the control group (90.8%). Non-use of zoledronic acid emerged as an independent risk factor for cage subsidence (OR = 6.047, P = 0.003), along with lower bone mineral density, lower postoperative anterior height, and concave endplate morphology. The model exhibited robust discriminative performance, with an area under the curve (AUC) of 0.872. CONCLUSION: The administration of zoledronic acid mitigates the risk of cage subsidence following OLIF combined with bilateral pedicle screw fixation in elderly patients; however, it does not improve the interbody fusion rate.

Complete chloroplast genome sequence of Thalictrum viscosum W.T.Wang & S.H.Wang, 1979 (Ranunculaceae).

Thalictrum viscosum W.T.Wang & S.H.Wang, 1979 is a flowering plant species in family Ranunculaceae that is endemic to Yunnan province of China. To facilitate genetic study of T. viscosum, we de novo assembled and annotated the complete chloroplast (cp) genome of T. viscosum for the first time. The total length of the cp genome of T. viscosum was 155,984 bp, with a GC content of 38.4%. The T. viscosum cp genome had a typical quadripartite structure with a large single-copy region of 85,339 bp, a small single-copy region of 17,656 bp, and a pair of inverted repeat regions of 26,495 bp. The cp genome consisted of 133 genes, including 87 protein-coding genes, 38 transfer RNA genes, and eight ribosomal RNA genes. We performed phylogenetic analysis of T. viscosum with the maximum-likelihood phylogenetic tree and indicated that T. viscosum was closely related to T. cirrhosum and T. foeniculaceum.

Comparative Analysis of Complete Chloroplast Genomes of Nine Species of Litsea (Lauraceae): Hypervariable Regions, Positive Selection, and Phylogenetic Relationships.

Litsea is a group of evergreen trees or shrubs in the laurel family, Lauraceae. Species of the genus are widely used for a wide range of medicinal and industrial aspects. At present, most studies related to the gene resources of Litsea are restricted to morphological analyses or features of individual genomes, and currently available studies of select molecular markers are insufficient. In this study, we assembled and annotated the complete chloroplast genomes of nine species in Litsea, carried out a series of comparative analyses, and reconstructed phylogenetic relationships within the genus. The genome length ranged from 152,051 to 152,747 bp and a total of 128 genes were identified. High consistency patterns of codon bias, repeats, divergent analysis, single nucleotide polymorphisms (SNP) and insertions and deletions (InDels) were discovered across the genus. Variations in gene length and the presence of the pseudogene ycf1Ψ, resulting from IR contraction and expansion, are reported. The hyper-variable gene rpl16 was identified for its exceptionally high Ka/Ks and Pi values, implying that those frequent mutations occurred as a result of positive selection. Phylogenetic relationships were recovered for the genus based on analyses of full chloroplast genomes and protein-coding genes. Overall, both genome sequences and potential molecular markers provided in this study enrich the available genomic resources for species of Litsea. Valuable genomic resources and divergent analysis are also provided for further research of the evolutionary patterns, molecular markers, and deeper phylogenetic relationships of Litsea.

Complete chloroplast genome sequence and annotation of Machilus salicina Hance, 1885 (lauraceae).

Machilus salicina Hance, 1885 is a species of flowering plant in the family Lauraceae and is mainly found at low altitudes in southern China. In this study, we assembled and annotated the complete chloroplast genome of M. salicina for the first time. We analyzed the general features of M. salicina and constructed a phylogenetic tree based on 15 Lauraceae species. The chloroplast genome of M. salicina had a total length of 153,943 bp. The length of a large single copy region, a small single copy region, and two inverted repeat regions were 93,689 bp, 20,070 bp, and 20,092bp, respectively. A total of 128 genes were detected, which included 84 protein-coding genes, 36 tRNAs and 8 rRNAs. The GC content of M. salicina complete chloroplast genome was 39.1%. The phylogenetic tree indicated that M. salicina was closely related to M. yunnanensis.

Galangin attenuates IL-1ß-induced catabolism in mouse chondrocytes and ameliorates murine osteoarthritis.

OBJECTIVE: Osteoarthritis (OA) is one of the most common chronic diseases, which is characterized by cartilage degeneration, subchondral osteosclerosis, and synovitis. Accumulating evidence has shown that galangin, a flavonoid derived from medicinal herbs, exhibits numerous pharmacological activities in various diseases. This study aimed to investigate the effects of galangin on interleukin (IL)-1ß-induced inflammation in mouse chondrocytes and explore the underlying mechanisms. METHODS: In this study, we investigated the protective effects of galangin on IL-1ß-induced inflammatory response in vitro using the CCK-8 assay, RT-qPCR, western blotting, and immunofluorescence staining. In addition, the therapeutic effects of galangin on the anterior cruciate ligament transection (ACLT) mouse model were also explored in vivo. Results: Galangin treatment suppressed the expression of IL-1ß-induced inflammatory cytokines, such as nitric oxide synthase, cyclooxygenase-2, TNF-α, and IL-6. Furthermore, galangin attenuated hypertrophic conversion and the extracellular matrix degradation via inhibiting the expression of catabolic enzymes. Mechanistically, galangin inhibited the activation of the JNK and ERK MAPK pathways and nuclear factor kappa-B (NF-κB) signaling pathway. In addition, galangin treatment ameliorated cartilage degeneration in an OA model in vivo. Conclusion: Galangin suppressed the IL-ß-induced inflammatory response in vitro and ameliorated cartilage degeneration in vivo via inhibiting the NF-κB pathway and JNK and ERK pathways, suggesting its potential as an effective candidate for the treatment of OA.

Factors related to perceived stress during the COVID-19 epidemic context among the general population in China: A cross-sectional nationwide study.

BACKGROUND: This study aimed to investigate factors related to high stress levels among the general population in China during the novel coronavirus disease (COVID-19) pandemic when its containment measures were in place and to identify the most stressed populations. METHODS: A nationwide study was conducted online among 5,039 adults in all 31 provinces in mainland China between March 1 and March 16, 2020. Bivariate analysis and multivariate logistic regressions were performed to explore the related factors of high perceived stress. RESULTS: Among all respondents, 36.0% reported a high level of stress. Respondents in Hubei province (the epicenter) were more likely to report high stress levels than those in low epidemic areas. Respondents who went outside every day or every other day reported greater odds of experiencing a high level of stress than those who went outside every 8-14 days. People with higher risk perceptions were more prone to report high stress levels. Respondents aged 16-35 were more likely to report high stress than respondents aged 46 or older. Lower household income and lower health literacy were related to increased odds of reporting high stress levels. LIMITATIONS: We used a convenience sample and self-reported survey data. CONCLUSIONS: We identified risk factors for high stress levels related to the epidemic (epidemic intensity in residential areas, risk perception, and frequency of going outside) and other vulnerabilities (younger age, low household income, low health literacy). Our findings can directly inform interventions and policies for mitigating stress among the general population for this or future epidemics.

TAZ inhibits osteoclastogenesis by attenuating TAK1/NF-κB signaling.

Osteoporosis is an osteolytic disorder commonly associated with excessive osteoclast formation. Transcriptional coactivator with PDZ-binding motif (TAZ) is a key downstream effector of the Hippo signaling pathway; it was suggested to be involved in the regulation of bone homeostasis. However, the exact role of TAZ in osteoclasts has not yet been established. In this study, we demonstrated that global knockout and osteoclast-specific knockout of TAZ led to a low-bone mass phenotype due to elevated osteoclast formation, which was further evidenced by in vitro osteoclast formation assays. Moreover, the overexpression of TAZ inhibited RANKL-induced osteoclast formation, whereas silencing of TAZ reduced it. Mechanistically, TAZ bound to TGF-activated kinase 1 (TAK1) and reciprocally inhibited NF-κB signaling, suppressing osteoclast differentiation. Collectively, our findings highlight an essential role of TAZ in the regulation of osteoclastogenesis in osteoporosis and its underlying mechanism.

Pristimerin Inhibits Osteoclast Differentiation and Bone Resorption in vitro and Prevents Ovariectomy-Induced Bone Loss in vivo.

INTRODUCTION: Osteoporosis is a metabolic bone disease characterized by reduced bone quantity and microstructure, typically owing to increased osteoclastogenesis and/or enhanced osteoclastic bone resorption, resulting in uncontrolled bone loss, which primarily affects postmenopausal women. In consideration of the severe side effects of current drugs for osteoporosis, new safe and effective medications are necessary. Pristimerin (Pri), a quinone methide triterpene extracted from Celastraceae and Hippocrateaceae members, exhibits potent antineoplastic and anti-inflammatory effects. However, its effect on osteoclasts remains unknown. MATERIALS AND METHODS: We evaluated the anti-osteoclastogenic and anti-resorptive effect of Pri on bone marrow-derived osteoclasts and its underlying mechanism in vitro. In addition, the protective effect of Pri on ovariectomy model was also explored in vivo. RESULTS: In vitro, Pri inhibited osteoclast differentiation and mature osteoclastic bone resorption in a time- and dose-dependent manner. Further, Pri suppressed the expression of osteoclast-related genes and the activation of key proteins. Pri also inhibited the early activation of ERK, JNK MAPK, and AKT signaling pathways in bone marrow-derived macrophages (BMMs), ultimately inhibiting the induction and activation of the crucial osteoclast transcriptional factor nuclear factor of activated T-cell cytoplasmic 1 (NFATc1). In vivo, consistent with our in vitro data, Pri clearly prevented ovariectomy-induced bone loss. CONCLUSION: Our data showed that Pri inhibits the differentiation and activation of osteoclasts in vitro and in vivo, and could be a promising candidate for treating osteoporosis.

Sarsasapogenin Suppresses RANKL-Induced Osteoclastogenesis in vitro and Prevents Lipopolysaccharide-Induced Bone Loss in vivo.

INTRODUCTION: Osteoclasts are giant polynuclear cells; their main function is bone resorption. An increased number of osteoclasts and enhanced bone resorption exert significant effects on osteoclast-related bone-lytic diseases, including osteoporosis. Given the limitations of current therapies for osteolytic diseases, it is urgently required to develop safer and more effective alternatives. Sarsasapogenin, a major sapogenin from Anemarrhena asphodeloides Bunge, possesses potent antitumor effects and inhibits NF-κB and MAPK signaling. However, the manner in which it affects osteoclasts is unclear. METHODS: We investigated the effects of anti-osteoclastogenic and anti-resorptive of sarsasapogenin on bone marrow-derived osteoclasts. RESULTS: Sarsasapogenin inhibited multiple RANKL-induced signaling cascades, thereby inhibiting the induction of key osteoclast transcription factor NFATc1. The in vivo and in vitro results were consistent: sarsasapogenin treatment protected against bone loss in a mouse osteolysis model induced by lipopolysaccharide. CONCLUSION: Our research confirms that sarsasapogenin can be used as a new treatment for osteoclast-related osteolytic diseases.

Oblique lumbar interbody fusion for adjacent segment disease after posterior lumbar fusion: a case-controlled study.

BACKGROUND: This study assessed clinical and radiographic outcomes of oblique lumbar interbody fusion (OLIF) in comparison with posterior reoperation for adjacent segment disease (ASD). METHODS: A total of 26 patients with symptomatic ASD after lumbar fusion were included in this retrospective case-controlled study conducted from January 2013 to December 2018. Twelve patients underwent single-segment OLIF with or without posterior instrumentation (OLIF group), whereas 14 patients underwent posterior reoperation (posterior approach group). The clinical outcomes included operative time, blood loss, hospital stay, Visual Analogue Scale (VAS), Oswestry Disability Index (ODI), and complications. Preoperative and postoperative radiographic outcomes were compared. RESULTS: The operative time (60.6 ± 16.1 min vs. 150.9 ± 28.5 min, respectively; P < 0.05) and the blood loss in the OLIF group 89.2 ± 49.0 ml vs. 340.7 ± 130.2 ml, respectively; P < 0.05) were significantly lower than those in the posterior group. The hospital stay was lower in the OLIF group than in the posterior approach group (6.6 ± 1.3 days vs. 9.5 ± 2.5 days, respectively; P < 0.05). In the posterior approach group, 6 of 14 patients (42.8%) had issue with dural tear, while none in the OLIF group had such issue (P < 0.05). The ODI score (13.2 ± 4.2 vs. 19.2 ± 7.2, respectively; P = 0.014) and the VAS back pain score were lower in the OLIF group postoperatively and at last follow-up. In the OLIF group, the radiographic outcomes were significantly improved postoperatively. CONCLUSIONS: Due to our results and early experiences, we proposed that OLIF was safe and effective for ASD. Compared with posterior reoperation, OLIF results in shorter operative time and hospital stay, lesser blood loss, and lower risk of dural injury.

Anacardic acid inhibits RANKL-induced osteoclastogenesis in vitro and prevents ovariectomy-induced bone loss in vivo.

Postmenopausal osteoporosis is the most common form of primary osteoporosis, and the incidence of the condition is rapidly increasing. In consideration of the limitations of current therapeutic options for the treatment of postmenopausal osteoporosis, there is an urgent need to develop safer alternatives. Anacardic acid, a natural phenolic acid compound extracted from cashew nut shell, possesses potent antitumor and anti-inflammatory effects and inhibits NF-κB signaling. However, its effect on osteoclasts remains unknown. This study reports the first evidence for the antiosteoclastogenic and antiresorptive effects of anacardic acid on bone marrow-derived macrophage-derived osteoclasts. Mechanistically, anacardic acid disrupts the phosphorylation of TGF-ß activated kinase 1 and subsequently suppresses multiple receptor activator of NF-κB ligand-induced signaling cascades, ultimately inhibiting the induction and activation of the crucial osteoclast transcriptional factor nuclear factor of activated T-cell cytoplasmic 1. Consistent with cellular results in vitro, anacardic acid treatment improves bone density in the murine model of ovariectomy-induced bone loss. Taken together, our study provides promising evidence for the therapeutic application of anacardic acid as a new potential pharmacological treatment for osteoporosis.-Zhao, K., Jia, Y., Peng, J., Pang, C., Zhang, T., Han, W., Jiang, J., Lu, X., Zhu, J., Qian, Y. Anacardic acid inhibits RANKL-induced osteoclastogenesis in vitro and prevents ovariectomy-induced bone loss in vivo.

Psoralen accelerates bone fracture healing by activating both osteoclasts and osteoblasts.

Bone fracture healing is a complex, dynamic process that involves various cell types, with osteoclasts and osteoblasts playing indispensable roles. In this study, we found that psoralen, the main active ingredient in Psoralea corylifolia L. fruit extract, enhanced bone fracture healing through activation of osteoclast and osteoblast activity via the ERK signaling pathway. In detail, psoralen promoted receptor activator of nuclear factor-κB ligand-induced osteoclastogenesis, mRNA expression of osteoclast-specific genes, and osteoclastic bone resorption in primary bone marrow-derived macrophages. Meanwhile, psoralen induced osteogenic differentiation by promoting the mRNA expression of the osteoblast differentiation markers alkaline phosphatase, runt-related transcription factor 2, osterix, and osteocalcin. At the molecular level, psoralen preferentially activated ERK1/2 but not JNK or p38 MAPKs. Further experiments revealed that psoralen-induced osteoclast and osteoblast differentiation was abrogated by a specific inhibitor of phosphorylated ERK. In addition, psoralen accelerated bone fracture healing in a rat tibial fracture model, and the numbers of osteoclasts and osteoblasts were increased in psoralen-treated fracture callus. Taken together, our findings indicate that psoralen accelerates bone fracture healing through activation of osteoclasts and osteoblasts via ERK signaling and has potential as a novel drug in the orthopedic clinic for the treatment of bone fractures.-Zhang, T., Han, W., Zhao, K., Yang, W., Lu, X., Jia, Y., Qin, A., Qian, Y. Psoralen accelerates bone fracture healing by activating both osteoclasts and osteoblasts.

Deguelin inhibits RANKL-induced osteoclastogenesis in vitro and prevents inflammation-mediated bone loss in vivo.

Excessive bone resorption by osteoclasts (OCs) plays an important role in lytic bone diseases, such as osteoporosis. Although the pharmacological treatment of osteoporosis has been extensively developed, alternative treatments are still needed. Deguelin, a rotenoid isolated from several plant species, is a strong antitumor agent; however, its effect on OCs remains unclear. To the best of our knowledge, this is the first study to report that deguelin inhibits the receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL)-induced osteoclastogenesis, messenger RNA expression of osteoclastic-specific genes, and osteoclastic bone resorption, in primary bone marrow-derived macrophages. At the molecular level, deguelin markedly blocked RANKL-induced osteoclastogenesis by attenuating the phosphorylation of NF-κB p65 and inhibiting p65 nuclear translocation. In addition, deguelin suppressed the downstream expression of nuclear factor of activated T-cell cytoplasmic 1, which is a crucial transcription factor in OC differentiation. Consistent with the in vitro results, deguelin inhibited lipopolysaccharide-induced bone resorption by suppressing osteoclastogenesis. Taken together, our findings reveal that deguelin has antiosteoclastic effects in vitro and in vivo and possesses potential as a new therapeutic option for osteolytic bone diseases.

Garcinol suppresses RANKL-induced osteoclastogenesis and its underlying mechanism.

Osteoclasts (OCs) are multinuclear giant cells responsible for bone resorption, and an excessive bone resorption by OCs plays an important role in osteoporosis. Commonly used drugs for the treatment of osteoporosis have severe side effects. As such, identification of alternative treatments is essential. Garcinol, a polyisoprenylated benzophenone extracted from the fruit of Garcinia indica, has shown a strong antitumor effect through the nuclear factor-κB (NF-κB) and mitogen-associated protein kinases (MAPK) signaling pathways. However, the role of garcinol in the osteoclastogenesis is still unclear. Here, we demonstrated that garcinol can inhibit the receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis, osteoclastogenesis-related gene expression, the f-actin ring, and resorption pit formation. In addition, garcinol abrogated RANKL-induced osteoclastogenesis by attenuating the degradation of the MAPK, NF-κB, and PI3K-AKT signaling pathway as well as downstream factors c-jun, c-fos, and NFATC1. In vivo, suppression of osteoclastogenesis by garcinol was evidenced by marked inhibition of lipopolysaccharide-induced bone resorption. In conclusion, our data demonstrated that garcinol inhibited the RANKL-induced osteoclastogenesis by suppressing the MAPK, NF-κB, and PI3K-AKT signaling pathways and thus has potential as a novel therapeutic option for osteolytic bone diseases.

Dual effects of baicalin on osteoclast differentiation and bone resorption.

Osteoclasts (OC) are critical cells responsible for many bone diseases such as osteoporosis. It is of great interest to identify agents that can regulate the activity of OC to treat osteolytic bone diseases. In this study, we found that baicalin exerted a two-way regulatory effect on OC in a concentration-dependent manner in vitro and in vivo. In detail, baicalin at a low concentration (below 1 µmol/L) enhanced OC differentiation and bone resorption, but baicalin at a high concentration (above 2 µmol/L) exhibited inhibitory effects on OC. We demonstrated that baicalin at low concentrations enhanced the mitogen-activated protein kinase (MAPK) (ERK) signalling pathway and activated c-Fos and NFATc1 expression, and thus enhanced gene expression, OC differentiation and bone resorption. However, baicalin at higher levels not only suppressed ERK phosphorylation and c-fos and NFATc1 expression, but also altered the expression of apoptosis-related proteins, and therefore inhibiting OC function. This dual effect was further verified in an LPS-induced mouse calvarial osteolysis model, evidenced by enhanced osteolysis at a lower concentration but reduced bone loss at a higher concentration. Overall, our findings indicate that baicalin exerts dose-dependent effects on OC formation and function. Therefore, caution should be applied when using baicalin to treating OC-related bone diseases.

The emerging role of Hippo signaling pathway in regulating osteoclast formation.

A delicate balance between osteoblastic bone formation and osteoclastic bone resorption is crucial for bone homeostasis. This process is regulated by the Hippo signaling pathway including key regulatory molecules RASSF2, NF2, MST1/2, SAV1, LATS1/2, MOB1, YAP, and TAZ. It is well established that the Hippo signaling pathway plays an important part in regulating osteoblast differentiation, but its role in osteoclast formation and activation remains poorly understood. In this review, we discuss the emerging role of Hippo-signaling pathway in osteoclast formation and bone homeostasis. It is revealed that specific molecules of the Hippo-signaling pathway take part in a stage specific regulation in pre-osteoclast proliferation, osteoclast differentiation and osteoclast apoptosis and survival. Upon activation, MST and LAST, transcriptional co-activators YAP and TAZ bind to the members of the TEA domain (TEAD) family transcription factors, and influence osteoclast differentiation via regulating the expression of downstream target genes such as connective tissue growth factor (CTGF/CCN2) and cysteine-rich protein 61 (CYR61/CCN1). In addition, through interacting or cross talking with RANKL-mediated signaling cascades including NF-κB, MAPKs, AP1, and NFATc1, Hippo-signaling molecules such as YAP/TAZ/TEAD complex, RASSF2, MST2, and Ajuba could also potentially modulate osteoclast differentiation and function. Elucidating the roles of the Hippo-signaling pathway in osteoclast development and specific molecules involved is important for understanding the mechanism of bone homeostasis and diseases.

Fangchinoline suppresses the proliferation, invasion and tumorigenesis of human osteosarcoma cells through the inhibition of PI3K and downstream signaling pathways.

Osteosarcoma is the most common malignant bone tumor. Most patients diagnosed with osteosarcoma are less than 20 years of age. Osteosarcoma cells proliferate rapidly and invade other tissues. At present, neoadjuvant chemotherapy is the primary pharmacodynamic strategy to prevent the progression of osteosarcoma. However, adverse effects of this strategy limit its long­term application. Previous research has shown that fangchinoline exerts antitumor effects on several types of tumor cells; however, its effect on osteosarcoma cells remains unknown. The present study evaluated the effects of fangchinoline on the proliferation, apoptosis, migration and invasion of osteosarcoma cells in vitro and on their tumorigenesis in vivo and determined the possible underlying mechanism of action. Fangchinoline­treated MG63 and U20S cells showed significantly decreased proliferation and significantly increased apoptosis. Fangchinoline markedly suppressed the migration and invasion of the MG63 cells. Fangchinoline­treated MG63 cells showed significantly decreased expression of phosphoinositide 3­kinase (PI3K) and Aktp­Thr308. Moreover, fangchinoline­treated MG63 cells showed downregulated expression of cyclin D1 and matrix metalloproteinase 2 and 9, which act downstream of PI3K, and upregulated expression of caspase­3 and caspase­8. Furthermore, fangchinoline suppressed the growth of subcutaneous osteosarcoma tumors in Balb/c mice subcutaneously injected with osteosarcoma cells. These findings suggest that fangchinoline inhibits the progression of osteosarcoma by suppressing the proliferation, migration and invasion and by accelerating the apoptosis of osteosarcoma cells. In addition, our results suggest that the mechanism underlying the antitumor effects of fangchinoline involve the inhibition of PI3K and its downstream signaling pathways.

Galangin suppresses human osteosarcoma cells: An exploration of its underlying mechanism.

Osteosarcoma is the most common malignant bone tumor that frequently affects adolescents. Osteosarcoma cells tend to proliferate and invade other tissues such as those of the lungs. Currently, neoadjuvant chemotherapy is the primary strategy to prevent tumor progression. However, its adverse effects result in poor long-term outcomes. Previous research has shown that galangin exhibits antitumor properties on several types of cancer cells; however its effect on osteosarcoma cells is yet unknown. The aims of this study were to evaluate the effects of galangin on the proliferation, apoptosis, migration, and invasion of osteosarcoma cells and to explore the underlying mechanisms. We found that the proliferation of MG63 and U20S osteosarcoma cells decreased significantly, while the apoptosis of MG63 cells accelerated significantly after exposure to galangin. In addition, the migration and invasion of MG63 cells were significantly inhibited by galangin. Moreover, phosphoinositide 3-kinase (PI3K) and Aktp-Thr308 expression levels were found to be significantly lower in galangin-treated MG63 cells than in the control cells, and the protein expression levels of their downstream regulators cyclin D1 and matrix metalloproteinase 2/9 were also downregulated in galangin-treated groups, while those of p27Kip1, caspase-3, and caspase-8 were upregulated. These findings suggest that galangin suppresses osteosarcoma cells by inhibiting their proliferation and invasion and accelerating their apoptosis, and the mechanism may be associated with the inhibition of PI3K and its downstream signaling pathway.

The osteogenic potential of human bone callus.

Bone callus, generated during fracture healing, is commonly discarded during surgical procedures. The aim of this study was to investigate the osteogenic potential of bone callus and its possible use as autograft material for patients needing bone grafts. Histology, immunohistochemistry, micro-computed tomography, and biomechanics were performed to examine osteogenic cells, osteoinductive factors, and the osteoconductive structure of bone callus. Alkaline phosphatase-positive osteoblasts, osteoinductive factors (including BMP2, FGF2, TGFB1, and IGF1), and a porous structure were found in bone callus. Early-stage callus (within 3 months after fracture) presented significantly improved osteogenic properties compared to medium- (3-9 months) and late-stage (longer than 9 months) callus. The results revealed that bone callus induced new bone formation in a nude mouse model. Early-stage callus showed better performance to medium- and late-stage callus in the induction of new bone formation at both 8 and 12 weeks. These findings indicated that bone callus, especially early-stage callus, possesses osteogenic potential and can potentially serve as an alternative source of material for bone grafts.

Surface topography of hydroxyapatite promotes osteogenic differentiation of human bone marrow mesenchymal stem cells.

Effective and safe induction of osteogenic differentiation is one of the key elements of bone tissue engineering. Surface topography of scaffold materials was recently found to promote osteogenic differentiation. Utilization of this topography may be a safer approach than traditional induction by growth factors or chemicals. The aim of this study is to investigate the enhancement of osteogenic differentiation by surface topography and its mechanism of action. Hydroxyapatite (HA) discs with average roughness (Ra) of surface topography ranging from 0.2 to 1.65 µm and mean distance between peaks (RSm) ranging from 89.7 to 18.6 µm were prepared, and human bone-marrow mesenchymal stem cells (hBMSCs) were cultured on these discs. Optimal osteogenic differentiation was observed on discs with surface topography characterized by Ra ranging from 0.77 to 1.09 µm and RSm ranging from 53.9 to 39.3 µm. On this surface configuration of HA, hBMSCs showed oriented attachment, F-actin arrangement, and a peak in the expression of Yes-associated protein (YAP) and PDZ binding motif (TAZ) (YAP/TAZ). These results indicated that the surface topography of HA promoted osteogenic differentiation of hBMSCs, possibly by increasing cell attachment and promoting the YAP/TAZ signaling pathway.