[Corrigendum] Anti­osteoporotic effects of tetramethylpyrazine via promoting osteogenic differentiation and inhibiting osteoclast formation.

Subsequently to the publication of the above paper, an interested reader drew to the authors' attention that, in Fig. 2A on p. 8311, portraying the results of immunostaining experiments for osterix, the 'GIOP' and 'GIOP+TMP (20)' data panels contained overlapping data, such that these images were derived from apparently the same original source, where they were intended to show the results from differently performed experiments. Moreover, in Fig. 3A on p. 8312 showing the results from ALP staining and Alizarin Red S staining experiments, two pairs of apparently overlapping data panels were identified in the Dex 106 M / TMP 50 µM, 100 µM and 200 µM data panels. After having re­examined their original data, the authors have realized that the data featured in Figs. 2A and 3A were assembled incorrectly in these figures. Revised versions of Fig. 2 and 3, now containing replacement data for the experiments shown in Figs. 2A and 3A, are shown on the next page. Note that these errors did not adversely affect either the results or the overall conclusions reported in this study. All the authors agree with the publication of this corrigendum, and are grateful to the Editor of Molecular Medicine Reports for allowing them the opportunity to publish this. They also wish to apologize to the readership of the Journal for any inconvenience caused. [Molecular Medicine Reports 16: 8307­8314, 2017; DOI: 10.3892/mmr.2017.7610].

Author Correction: GPR120: A bi-potential mediator to modulate the osteogenic and adipogenic differentiation of BMMSCs.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

LncRNA SNHG5: A new budding star in human cancers.

Long non-coding RNA (LncRNA) belongs to non-coding RNAs longer than 200 nucleic acids. More and more studies have revealed that lncRNA can participate in the occurrence and pathophysiology of diseases, especially in cancers. Although research on lncRNAs has doubled year by year, little is known about the specific regulatory mechanisms of lncRNAs in diseases. The main purpose of this review is to explore the molecular mechanism and clinical significance of SNHG5 in cancers. We systematically search Pubmed to obtain relevant literature on SNHG5. In this review, the functional role, molecular mechanism, and clinical significance of SNHG5 in human cancers are described in detail. Small nucleolar RNA host gene 5 (SNHG5) has been shown to be involved in the development and tumorigenesis of a variety of cancers (colorectal, bladder, gastric, endometrial, acute lymphocytic leukemia, osteosarcoma, etc.). Its disorder is closely related to metastasis, pathological staging, and prognosis. LncRNA SNHG5 might be a potential and novel diagnostic marker for cancer patients, a target for molecular targeted therapy, and a prognostic diagnostic marker.

Anti­osteoporotic effects of tetramethylpyrazine via promoting osteogenic differentiation and inhibiting osteoclast formation.

Long­term glucocorticoid therapy results in various side effects, including a high incidence of glucocorticoid­induced osteoporosis (GIOP), which is the most common form of secondary osteoporosis. Excess glucocorticoids reduce the viability of bone marrow­derived mesenchymal stem cells (BMSCs) and prolong osteoclast survival. These two types of cell are essential in the balance between bone formation and resorption. Tetramethylpyrazine (TMP), the pharmacologically active component extracted from Chuanxiong, has been reported to protect BMSCs from glucocorticoid­induced apoptosis. In the present study, the protective effects of TMP on BMSC differentiation and osteoclasts maturation in GIOP were investigated in vivo and in vitro. The immunostaining of osterix (OSX) and tartrate­resistant acid phosphatase (TRAP) staining indicated that TMP promoted osteogenesis and inhibited osteoclastogenesis in a rat model of GIOP. Treatment with 10­6 M dexamethasone (Dex) significantly inhibited BMSC differentiation and increased TRAP­positive cells in vitro. However, different concentrations of TMP (50, 100 and 200 µM) ameliorated the negative effects of Dex by promoting the activity of alkaline phosphatase (ALP) and the calcium mineralization of BMSCs following osteogenic induction, which increased the expression levels of osteogenic genes, including ALP, collagen type I α1, osteocalcin and OSX, and decreased osteoclastogenesis­related genes, including TRAP, nuclear factor of T­cells cytoplasmic 1 and cathepsin K. In addition, it was found that the inhibition of receptor activator of nuclear factor­κB ligand and intereleukin­6 in BMSCs may be a possible mechanism for the protective effects of TMP against glucocorticoid­induced osteoclastogenesis. These results are the first, to the best of our knowledge, to demonstrate that TMP promotes BMSC differentiation and inhibits osteoclastogenesis to ameliorate bone mass change in GIOP.

Screening and validation of serum protein biomarkers for early postmenopausal osteoporosis diagnosis.

Postmenopausal osteoporosis is one of the most prominent worldwide public health problems and the morbidity is increasing with the aging population. It has been demonstrated that early diagnosis and intervention delay the disease progression and improve the outcome. Therefore, searching for biomarkers that are able to identify postmenopausal women at high risk for developing osteoporosis is an effective way to improve the quality of life of patients, and alleviate social and economic burdens. In the present study, a protein array was used to identify potential biomarkers. The bone mineral densities of 10 rats were dynamically measured in an ovariectomized model by micro­computed tomography assessment, and the early stage of osteoporosis was defined. Through the protein array­based screening, the expression levels of six serum protein biomarkers in ovariectomized rats were observed to alter at the initiation stage of the postmenopausal osteoporosis. Fractalkine, tissue inhibitor of metalloproteinases­1 and monocyte chemotactic protein­1 were finally demonstrated to be increased in the serum of eight enrolled postmenopausal osteoporosis patients using ELISA assay and were correlated with the severity of progressive bone loss. These biomarkers may be explored as potential early biomarkers to readily evaluate and diagnose postmenopausal osteoporosis in the clinic.

Tetramethylpyrazine Protects Against Glucocorticoid-Induced Apoptosis by Promoting Autophagy in Mesenchymal Stem Cells and Improves Bone Mass in Glucocorticoid-Induced Osteoporosis Rats.

Glucocorticoid-induced osteoporosis (GIOP) is a widespread clinical complication due to the common use of glucocorticoids. Excess glucocorticoids induce apoptosis of bone marrow-derived mesenchymal stem cells (BMSCs), which have been shown to play an increasingly important role in the pathogenesis and therapy of osteoporosis. Tetramethylpyrazine (TMP), an extract from one of the most recognized herbs in traditional Chinese medicine (Chuanxiong), has been reported to have antiapoptotic properties. In this study, we tested whether TMP protects rat BMSCs following exposure to glucocorticoids in vitro and in vivo. We treated BMSCs with different concentrations of TMP (50, 100, or 200 µM) and exposed them to 10-6 M dexamethasone (Dex) for 48 h in vitro. Our data showed that TMP inhibited Dex-induced cytotoxicity and protected BMSCs from apoptosis. Interestingly, further results demonstrated that TMP prevented apoptosis in BMSCs by promoting autophagy in an AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) pathway-dependent manner. In addition, calcein fluorescence double labeling and microcomputed tomography scanning indicated that 12 weeks of TMP administration augmented bone formation and protected trabecular bone mass in GIOP rats. We also discovered that first-passage BMSCs isolated from the TMP treatment group had a lower rate of apoptosis and a higher light chain 3 (LC3)-II/LC3-I ratio than the GIOP group. Our findings demonstrate for the first time that TMP can protect BMSCs from exposure to excess glucocorticoids by promoting autophagy through AMPK/mTOR pathway and might be an effective agent for the prevention and treatment of GIOP.

GPR120: A bi-potential mediator to modulate the osteogenic and adipogenic differentiation of BMMSCs.

Free fatty acids display diverse effects as signalling molecules through GPCRs in addition to their involvement in cellular metabolism. GPR120, a G protein-coupled receptor for long-chain unsaturated fatty acids, has been reported to mediate adipogenesis in lipid metabolism. However, whether GPR120 also mediates osteogenesis and regulates BMMSCs remain unclear. In this study, we showed that GPR120 targeted the bi-potential differentiation of BMMSCs in a ligand dose-dependent manner. High concentrations of TUG-891 (a highly selective agonist of GPR120) promoted osteogenesis via the Ras-ERK1/2 cascade, while low concentrations elevated P38 and increased adipogenesis. The fine molecular regulation of GPR120 was implemented by up-regulating different integrin subunits (α1, α2 and ß1; α5 and ß3). The administration of high doses of TUG-891 rescued oestrogen-deficient bone loss in vivo, further supporting an essential role of GPR120 in bone metabolism. Our findings, for the first time, showed that GPR120-mediated cellular signalling determines the bi-potential differentiation of BMMSCs in a dose-dependent manner. Additionally, the induction of different integrin subunits was involved in the cytoplasmic regulation of a seesaw-like balance between ERK and p38 phosphorylation. These findings provide new hope for developing novel remedies to treat osteoporosis by adjusting the GPR120-mediated differentiation balance of BMMSCs.

Prevalence of Coxsackievirus A6 and Enterovirus 71 in Hand, Foot and Mouth Disease in Nanjing, China in 2013.

BACKGROUND: Although hand, foot and mouth disease (HFMD) has been strongly associated with enterovirus 71 (EV71), coxsackievirus A16 (CVA16) and other enteroviruses, studies regarding coxsackievirus A6 (CVA6) infection in HFMD are limited. The aim of this study was to identify the major etiological agents causing HFMD in Nanjing in 2013 and explore the clinical and genetic characteristics of the prevalent enterovirus (EV) types in HFMD. METHODS: A total of 394 throat swabs were collected from hospitalized children diagnosed with HFMD from April to July 2013. EVs were detected by reverse transcription polymerase chain reaction of 5' UTR sequences. Genotyping and phylogenetic analysis were based on VP4 sequences. Demographic and clinical data were obtained. RESULTS: Of the specimens, 68.5% (270/394) were positive for EVs. The genotypes and detection rates were CVA6, 30.00% (81/270); EV71, 17.41% (47/270); HRV, 11.11% (30/270); CVA10, 3.33% (9/270); CVA2, 1.11% (3/270); CVA16, 0.74% (2/270); EV68, 0.37% (1/270); echovirus 6, 0.37% (1/270); echovirus 9, 0.37% (1/270), respectively. Patients infected with CVA6 displayed symptoms atypical of HFMD, including larger vesicles on their limbs and buttocks. Phylogenetic analysis revealed 2 genetically distinct CVA6 strains that circulated independently within the region. Patients infected with CVA6 were more likely to have abnormal periphery blood white blood cell and C-reactive protein levels, while EV71 was more likely to infect the central nervous system, as indicated by clinical manifestations and white blood cell analysis of cerebrospinal fluid. CONCLUSIONS: Multiple EV genotypes contributed to HFMD in Nanjing in 2013, and CVA6 was the dominant genotype. The clinical presentation of CVA6 infection differs from that of EV71 infection in HFMD.

Protective effects of myricitrin against osteoporosis via reducing reactive oxygen species and bone-resorbing cytokines.

Oxidative stress is a crucial pathogenic factor in the development of osteoporosis. Myricitrin, isolated from Myrica cerifera, is a potent antioxidant. We hypothesized that myricitrin possessed protective effects against osteoporosis by partially reducing reactive oxygen species (ROS) and bone-resorbing cytokines in osteoblastic MC3T3-E1 cells and human bone marrow stromal cells (hBMSCs). We investigated myricitrin on osteogenic differentiation under oxidative stress. Hydrogen peroxide (H2O2) was used to establish an oxidative cell injury model. Our results revealed that myricitrin significantly improved some osteogenic markers in these cells. Myricitrin decreased lipid production and reduced peroxisome proliferator-activated receptor gamma-2 (PPARγ2) expression in hBMSCs. Moreover, myricitrin reduced the expression of receptor activator of nuclear factor kappa-B ligand (RANKL) and IL-6 and partially suppressed ROS production. In vivo, we established a murine ovariectomized (OVX) osteoporosis model. Our results demonstrated that myricitrin supplementation reduced serum malondialdehyde (MDA) activity and increased reduced glutathione (GSH) activity. Importantly, it ameliorated the micro-architecture of trabecular bones in the 4th lumbar vertebrae (L4) and distal femur. Taken together, these results indicated that the protective effects of myricitrin against osteoporosis are linked to a reduction in ROS and bone-resorbing cytokines, suggesting that myricitrin may be useful in bone metabolism diseases, particularly osteoporosis.