Topiramate promotes osteogenic differentiation through AMPK-dependent phosphorylation of Smad1/5/9.

Topiramate [2,3:4,5-bis-o-(1-methylethylidene) β-D-fructo-pyranose sulfamate; TPM] is one of the most used new-generation antiepileptic drugs. It has been reported to regulate the differentiation of human bone cells. However, the molecular mechanism of TPM in osteoblast differentiation is not fully elucidated.

Policosanol Stimulates Osteoblast Differentiation via Adenosine Monophosphate-Activated Protein Kinase-Mediated Expression of Insulin-Induced Genes 1 and 2.

Policosanol is known as a hypocholesterolemic compound and is derived from plants such as sugar cane and corn. Policosanol can lower blood pressure or inhibit adipogenesis, but its effect on osteogenic differentiation and the molecular mechanism is unclear. This study aims to investigate the effect of policosanol on osteogenic differentiation in MC3T3-E1 cells and zebrafish models.

Eucalyptol induces osteoblast differentiation through ERK phosphorylation in vitro and in vivo.

Eucalyptol (EU) is monoterpene oxide that is the main component of the essential oil extracted from aromatic plants such as Eucalyptus globules. EU has therapeutic effects such as antibacterial, anti-inflammatory and antioxidant in chronic diseases including inflammation disorder, respiratory disease, and diabetic disease. However, the effects of EU on osteoblast differentiation and bone diseases such as osteoporosis have not been studied.

Zingerone stimulates osteoblast differentiation by increasing Smad1/5/9-mediated HO-1 expression in MC3T3-E1 cells and primary mouse calvarial cells.

Zingerone is a non-volatile compound found mainly in dried ginger. Zingerone increases the expression of osteogenic markers and has antioxidant effects. A previous study showed that zingerone accelerated osteoblast differentiation by suppressing the expression of Smad7, a member of the inhibitory Smad (I-Smad) family.

NXNL1 negatively regulates osteoblast differentiation via GDF15-induced PP2A Cα dependent manner in MC3T3-E1 cells.

Controlling the level of intracellular reactive oxygen species (ROS) is important for the survival and differentiation of osteoblasts. Intracellular ROS levels are controlled by antioxidant enzymes that modulate the redox state of the cell. Nucleoredoxin-like 1 (NXNL1) is an antioxidant enzyme that increases the viability of rod and cone cells by protecting them from oxidative stress, and is a potential pharmacological target for the treatment of retinitis pigmentosa.

Cip2A modulates osteogenic differentiation via the ERK-Runx2 pathway in MG63 cells.

Cancerous inhibitor of protein phosphatase 2A (Cip2A) is an oncoprotein that promotes the development of several types of cancer. However, its molecular function in osteoblast differentiation remains unclear. In this study, we found that Cip2A was upregulated under osteogenic conditions in MG63 cells.

Policosanol attenuates Pi-induced calcification via AMPK-mediated INSIGs expression in rat VSMCs.

Policosanol is a hypocholesterolemic derived from sugar cane and corn that downregulates blood cholesterol levels. It can further lower blood pressure and reduce liver inflammation. Policosanol can also affect vascular calcification, however, its molecular mechanisms are not well understood.

Zingerone Attenuates Pi-induced Vascular Calcification via AMPK-mediated TIMP4 Expression.

Objective: Vascular calcification requires the differentiation of vascular smooth muscle cells (VSMCs) into osteoblast-like cells. This phenomenon can be enhanced by inflammation and oxidative stress. Zingerone is one of the active ingredients present in the ginger plant that has anti-inflammatory and antioxidant effects.

Chrysophanol increases osteoblast differentiation via AMPK/Smad1/5/9 phosphorylation in vitro and in vivo.

Chrysophanol (Chrysophanic acid; CA) is a natural anthraquinone found in Senna tora and rhubarb that has various characteristic features, including the ability to suppress adipogenesis. However, its effects on osteoblast differentiation have not been investigated. Herein, this study aimed to demonstrate the mechanism by which CA induces the osteoblast differentiation.

Vitexin enhances osteoblast differentiation through phosphorylation of Smad and expression of Runx2 at in vitro and ex vivo.

Vitexin (apigenin-8-C-d-glucopyranoside) is a flavonoid isolated from natural sources. It has been employed as an anti-oxidant, anti-inflammatory, and anti-cancer agent, and is used as a traditional Chinese medicine to treat a variety of illnesses. The present study investigated the effect of vitexin on osteoblast differentiation of C3H10T1/2 mesenchymal stem cells, MC3T3-E1 preosteoblast, mouse calvarial primary cells, and primary bone marrow stem cells (BMSCs).

Therapeutic anti-psoriatic effects of myeloid-derived suppressor cells in combination with systemic tacrolimus (FK-506) in an imiquimod-induced mouse model of psoriasis.

Although tacrolimus (FK-506) has been shown to be an effective monotherapy for psoriasis, it does not always work well. Currently, combination therapy is frequently used to manage psoriasis because clinical trials have shown it may provide additive or synergistic benefits and reduce risks of adverse effects. Myeloid-derived suppressor cells (MDSCs) have potent immunomodulatory and anti-inflammatory properties in autoimmune diseases.

Carbohydrate responsive element binding protein (ChREBP) negatively regulates osteoblast differentiation via protein phosphatase 2A Cα dependent manner.

Carbohydrate responsive element binding protein (ChREBP) is a major transcription factor of lipogenesis regulated by glucose status in the liver. However, the function of ChREBP in osteogenic differentiation is unclear. The present study examined the role of ChREBP in osteoblast differentiation in MC3T3-E1 preosteoblast cell line.

Fat Mass and Obesity-Associated (FTO) Stimulates Osteogenic Differentiation of C3H10T1/2 Cells by Inducing Mild Endoplasmic Reticulum Stress via a Positive Feedback Loop with p-AMPK.

Fat mass and obesity-associated (FTO) gene helps to regulate energy homeostasis in mammals by controlling energy expenditure. In addition, FTO functions in the regulation of obesity and adipogenic differentiation; however, a role in osteogenic differentiation is unknown. This study investigated the effects of FTO on osteogenic differentiation of C3H10T1/2 cells and the underlying mechanism.

Alpha-pinene promotes osteoblast differentiation and attenuates TNFα-induced inhibition of differentiation in MC3T3-E1 pre-osteoblasts.

Alpha-pinene (α-pinene) is an organic compound, found in the oils of many species of coniferous trees, especially pine. α-Pinene reportedly has antioxidant and anti-inflammatory activities; however, its effects on osteoblasts are unknown. This study investigated the effects of α-pinene on osteoblast differentiation and tumour necrosis factor-alpha (TNFα)-induced inhibition of osteogenesis.

Fenofibrate induces PPARα and BMP2 expression to stimulate osteoblast differentiation.

The peroxisome proliferator-activated receptor (PPAR)-α agonist fenofibrate is used as a lipid-lowering agent to reduce cholesterol and triglyceride in blood. In this study, we investigated whether fenofibrate affects osteoblast differentiation of osteogenic precursor cells. Quantitative real-time PCR and alkaline phosphatase (ALP) staining assays revealed that fenofibrate can enhance the osteoblast differentiation of C3H10T1/2 and MC3T3-E1 cells.

Peroxiredoxin II negatively regulates BMP2-induced osteoblast differentiation and bone formation via PP2A Cα-mediated Smad1/5/9 dephosphorylation.

Peroxiredoxin II (Prx II), an antioxidant enzyme in the Prx family, reduces oxidative stress by decreasing the intracellular ROS levels. Osteoblast differentiation is promoted by bone morphogenetic protein 2 (BMP2), which upregulates the expression of osteoblast differentiation marker genes, through Smad1/5/9 phosphorylation. We found that Prx II expression was increased by a high dose of lipopolysaccharide (LPS) but was not increased by a low dose of LPS.

Estradiol-induced RORα expression positively regulates osteoblast differentiation.

The retinoic acid receptor-related orphan receptor alpha (RORα) is a member of the nuclear hormone receptor superfamily. Several studies show that estradiol is related to RORα expression. However, the link between estradiol and RORα in osteoblast differentiation remains unknown.

OVO homologue-like 1 promotes osteoblast differentiation through BMP2 expression.

OVO homologue-like 1 (OVOL1) encodes a C2H2 zinc finger protein and is an evolutionarily conserved gene in mammals. The OVOL1 expression is required for development. However, the function of OVOL1 in bone metabolism remains unreported.

CRTC2 suppresses BMP2-induced osteoblastic differentiation via Smurf1 expression in MC3T3-E1 cells.

Aims: CREB (cAMP response element-binding protein)-regulated transcription coactivator (CRTC2) has been reported to act as a coactivator of CREB during gluconeogenesis. The role of CRTC2 in osteoblastic differentiation has not yet been elucidated. The aim of this study is to identify the mechanism of CRTC2 in osteoblast differentiation.

Hypothermia-induced RNA-binding motif protein 3 (RBM3) stimulates osteoblast differentiation via the ERK signaling pathway.

The RNA-binding motif protein 3 (RBM3) belongs to a small group of proteins whose synthesis increases during hypothermia while global protein production is slowed down. Bone homeostasis is maintained by a balance between bone resorption and bone formation. Osteoblasts are key components of the bone and have an important role in bone remodeling cycle.

Kisspeptin-10 (KP-10) stimulates osteoblast differentiation through GPR54-mediated regulation of BMP2 expression and activation.

Kisspeptin-10 (KP-10) acts as a tumor metastasis suppressor via its receptor, G-protein-coupled receptor 54 (GPR54). The KP-10-GPR54 system plays an important role in embryonic kidney development. However, its function in osteoblast differentiation is unknown.

Curcumin induces osteoblast differentiation through mild-endoplasmic reticulum stress-mediated such as BMP2 on osteoblast cells.

Aims: Curcumin (diferuloylmethane or [1E,6E]-1,7-bis[4-hydroxy-3-methoxyphenyl]-1,6heptadiene-3,5-dione) is a phenolic natural product derived from the rhizomes of the turmeric plant, Curcuma longa. It is reported to have various biological actions such as anti-oxidative, anti-inflammatory, and anti-cancer effects. However, the molecular mechanism of osteoblast differentiation by curcumin has not yet been reported.

Piperine induces osteoblast differentiation through AMPK-dependent Runx2 expression.

Piperine is an alkaloid responsible for the pungency of black pepper and long pepper. It is reported to have various biological actions such as anti-oxidative and anti-inflammatory, and aids cancer prevention. Antioxidants have been shown to promote osteoblast differentiation.

Zaluzanin C (ZC) induces osteoblast differentiation through regulating of osteogenic genes expressions in early stage of differentiation.

Zaluzanin C (ZC) is a sesquiterpene lactones used in herbal medicines. This study examined the effects of ZC on osteoblast differentiation. ZC-induced mRNA expressions levels of osteogenic genes in C3H10T1/2 and MC3T3-E1 cells were determined by RT-PCR and qPCR.

Costunolide increases osteoblast differentiation via ATF4-dependent HO-1 expression in C3H10T1/2 cells.

Aims: Costunolide is a sesquiterpene lactones used in many herbal medicines, with well-established anti-inflammatory and anti-oxidant functions modulating endoplasmic reticulum (ER) stress pathways, and which promotes the expression of anti-oxidant genes. The aim of this study is to investigate whether costunolide is involved in osteoblast differentiation and, determine the mechanisms of differentiation in mesenchymal stem cells.

Main Methods: The cytotoxicity of costunolide was identified using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay.