Research Interests:
To investigate the effects and mechanisms of irisin, a newly discovered myokine, in cartilage development, osteoarthritis (OA) pathophysiology and its therapeutic potential for treating OA we applied the following five strategical... more
To investigate the effects and mechanisms of irisin, a newly discovered myokine, in cartilage development, osteoarthritis (OA) pathophysiology and its therapeutic potential for treating OA we applied the following five strategical analyses using (1) murine joint tissues at different developmental stages; (2) human normal and OA pathological tissue samples; (3) experimental OA mouse model; (4) irisin gene knockout (KO) and knock in (KI) mouse lines and their cartilage cells; (5) in vitro mechanistic experiments. We found that Irisin was involved in all stages of cartilage development. Both human and mouse OA tissues showed a decreased expression of irisin. Intra-articular injection of irisin attenuated ACLT-induced OA progression. Irisin knockout mice developed severe OA while irisin overexpression in both irisin KI mice and intraarticular injection of irisin protein attenuated OA progression. Irisin inhibited inflammation and promoted anabolism in chondrogenic ADTC5 cells. Prolifera...
Research Interests:
Balancing the process of bone formation and resorption is important in the maintenance of healthy bone. Therefore, the discovery of novel factors that can regulate bone metabolism remains needed. Irisin is a newly identified hormone‐like... more
Balancing the process of bone formation and resorption is important in the maintenance of healthy bone. Therefore, the discovery of novel factors that can regulate bone metabolism remains needed. Irisin is a newly identified hormone‐like peptide. Recent studies have reported the involvement of irisin in many physiological and pathological conditions with bone mineral density changes, including osteopenia and osteoporotic fractures. In this study, we generated the first line of Osx‐Cre:FNDC5/irisin KO mice, in which FNDC5/irisin was specifically deleted in the osteoblast lineage. Gene and protein expressions of irisin were remarkably decreased in bones but no significant differences in other tissues were observed in knockout mice. FNDC5/irisin deficient mice showed a lower bone density and significantly delayed bone development and mineralization from early‐stage to adulthood. Our phenotypical analysis exhibited decreased osteoblast‐related gene expression and increased osteoclast‐re...
Research Interests:
Research Interests:
Specific microRNAs (miRs) and the Wnt signaling pathway play critical roles in regulating bone development and homeostasis. Our previous studies revealed the ability of miR-335-5p to promote osteogenic differentiation by downregulating... more
Specific microRNAs (miRs) and the Wnt signaling pathway play critical roles in regulating bone development and homeostasis. Our previous studies revealed the ability of miR-335-5p to promote osteogenic differentiation by downregulating Wnt antagonist Dickkopf-1 (DKK1). The purpose of this study was to use nano-materials to efficiently deliver miR-335-5p into osteogenic cells for tissue engineering applications. We synthesized and screened a library of 12 candidate nano-lipidoids，of which L8 was identified as the preferred biodegradable lipidoid for miRNA molecule delivery into cells. We then investigated whether a lipidoid-miRNA formulation of miR-335-5-p (LMF-335) could successfully deliver miR-335-5-p into cells to promote osteogenesis in vitro and calvarial bone healing in vivo. Transfection of C3H10T1/2 cells and bone marrow stromal cells (BMSCs) with LMF-335 led to decreased expression of DKK1 and increased expression of the key osteogenic genes. LMF-335 and LMF-335-transfected...
Research Interests:
Irisin is a polypeptide hormone derived from the proteolytic cleavage of fibronectin-type III domain-containing 5 (FNDC5) protein. Once released to circulation upon exercise or cold exposure, irisin stimulates browning of white adipose... more
Irisin is a polypeptide hormone derived from the proteolytic cleavage of fibronectin-type III domain-containing 5 (FNDC5) protein. Once released to circulation upon exercise or cold exposure, irisin stimulates browning of white adipose tissue (WAT) and uncoupling protein 1 (UCP1) expression, leading to an increase in total body energy expenditure by augmented UCP1-mediated thermogenesis. It is currently unknown whether irisin is secreted by bone upon exercise or whether it regulates bone metabolism in vivo. In this study, we found that 2 weeks of voluntary wheel-running exercise induced high levels of FNDC5 messenger RNA as well as FNDC5/irisin protein expression in murine bone tissues. Increased immunoreactivity due to exercise-induced FNDC5/irisin expression was detected in different regions of exercised femoral bones, including growth plate, trabecular bone, cortical bone, articular cartilage, and bone–tendon interface. Exercise also increased expression of osteogenic markers in ...
Research Interests:
MicroRNAs (miRNAs) and the Wnt signaling pathway play critical roles in regulating bone development and homeostasis. Our previous study revealed high expression of miR-335-5p in osteoblasts and hypertrophic chondrocytes in mouse embryos... more
MicroRNAs (miRNAs) and the Wnt signaling pathway play critical roles in regulating bone development and homeostasis. Our previous study revealed high expression of miR-335-5p in osteoblasts and hypertrophic chondrocytes in mouse embryos and the ability of miR-335-5p to promote osteogenic differentiation by downregulating Wnt antagonist Dickkopf-1 (DKK1). The purpose of this study was to investigate the effects of miR-335-5p constitutive overexpression on bone formation and regeneration in vivo. To that end, we generated a transgenic mouse line specifically overexpressing miR-335-5p in osteoblasts lineage by the osterix promoter and characterized its bone phenotype. Bone histomorphometry and μCT analysis revealed higher bone mass and increased parameters of bone formation in transgenic mice than in wild-type littermates. Increased bone mass in transgenic mice bones also correlated with enhanced expression of osteogenic differentiation markers. Upon osteogenic induction, bone marrow s...
Research Interests:
DICER is the central enzyme that cleaves precursor microRNAs (miRNAs) into 21-25 nucleotide duplex in cell lineage differentiation, identity and survival. In the current study, we characterized the specific bone metabolism genes and... more
DICER is the central enzyme that cleaves precursor microRNAs (miRNAs) into 21-25 nucleotide duplex in cell lineage differentiation, identity and survival. In the current study, we characterized the specific bone metabolism genes and corresponding miRNAs and found that DICER and Runt-related transcription factor 2 (Runx2) expressions increased simultaneously during osteogenic differentiation. Luciferase assay showed that Runx2 significantly increased the expression levels of DICER luciferase promoter reporter. Our analysis also revealed weaker DICER expression in embryos of Runx2 knock out mice (Runx2 -/-) compared with that of Runx2 +/- and Runx2 +/+ mice. We further established the calvarial bone critical-size defect (CSD) mouse model. The bone marrow stromal cells (BMSCs) transfected with siRNA targeting DICER were combined with silk scaffolds and transplanted into calvarial bone CSDs. Five weeks post-surgery, micro-CT analysis revealed impaired bone formation and repairing in cal...
Research Interests:
Emerging evidence suggests an important role for epigenetic mechanisms in modulating signals during macrophage polarization and inflammation. JMJD3, a JmjC family histone demethylase necessary for M2 polarization is also required for... more
Emerging evidence suggests an important role for epigenetic mechanisms in modulating signals during macrophage polarization and inflammation. JMJD3, a JmjC family histone demethylase necessary for M2 polarization is also required for effective induction of multiple M1 genes by lipopolysaccharide (LPS). However, the effects of JMJD3 to inflammation in the context of obesity remains unknown. To address this deficiency, we firstly examined the expression of JMJD3 in macrophage isolated from bone marrow and adipose tissue of diet induced obesity (DIO) mice. The results indicated that JMJD3 was down-regulated in obesity. Adiponectin (APN), a factor secreted by adipose tissue which is down-regulated in obesity, functions to switch macrophage polarization from M1 to M2, thereby attenuating chronic inflammation. Intriguingly, our results indicated that APN contributed to JMJD3 up-regulation, reduced macrophage infiltration in obese adipose tissue, and abolished the up-regulation of JMJD3 in...
Research Interests: Biology, Inflammation, Immunohistochemistry, Macrophages, Innate immunity, and 15 moreMedicine, Adipose tissue, Mice, Macrophage, Animals, Cellular Physiology, Medical Physiology, Lipopolysaccharides, Adiponectin, Periodontitis, Protein Binding, Macrophage Polarization, Bone Resorption, PORPHYROMONAS GINGIVALIS, and Interferon regulatory factors
Adiponectin (APN) is an adipocyte-secreted adipokine that exerts well-characterized antidiabetic properties. Patients with type 2 diabetes (T2D) are characterized by reduced APN levels in circulation and impaired stem cell and progenitor... more
Adiponectin (APN) is an adipocyte-secreted adipokine that exerts well-characterized antidiabetic properties. Patients with type 2 diabetes (T2D) are characterized by reduced APN levels in circulation and impaired stem cell and progenitor cell mobilization from the bone marrow for tissue repair and remodeling. In this study, we found that APN regulates the mobilization and recruitment of bone marrow-derived mesenchymal stem cells (BMSCs) to participate in tissue repair and regeneration. APN facilitated BMSCs migrating from the bone marrow into the circulation to regenerate bone by regulating stromal cell-derived factor (SDF)−1 in a mouse bone defect model. More importantly, we found that systemic APN infusion ameliorated diabetic mobilopathy of BMSCs, lowered glucose concentration, and promoted bone regeneration in diet-induced obesity mice. In vitro studies allowed us to identify Smad1/5/8 as a novel signaling mediator of APN receptor (AdipoR)−1 in BMSCs and osteoblasts. APN stimula...
Research Interests: Endocrinology, Stem Cells, Biology, Cell Biology, Stem Cell, and 15 moreMedicine, Signal Transduction, Biological Sciences, Mesenchymal stem cells, Humans, Mice, Animals, Male, Adiponectin, Cell Proliferation, Mesenchymal Stromal Cells, Stem Cell Niche, Bone Marrow Cells, Bone Diseases, and Medical and Health Sciences
Adiponectin (APN), the most abundant adipocyte-secreted adipokine, regulates energy homeostasis and exerts well-characterized insulin-sensitizing properties. The peripheral or central effects of APN regulating bone metabolism are... more
Adiponectin (APN), the most abundant adipocyte-secreted adipokine, regulates energy homeostasis and exerts well-characterized insulin-sensitizing properties. The peripheral or central effects of APN regulating bone metabolism are beginning to be explored but are still not clearly understood. In the present study, we found that APN-knockout (APN-KO) mice fed a normal diet exhibited decreased trabecular structure and mineralization and increased bone marrow adiposity compared with wild-type (WT) mice. APN intracerebroventricular infusions decreased uncoupling protein 1 (UCP1) expression in brown adipose tissue, epinephrine and norepinephrine serum levels, and osteoclast numbers, whereas osteoblast osteogenic marker expression and trabecular bone mass increased in APN-KO and WT mice. In addition, centrally administered APN increased hypothalamic tryptophan hydroxylase 2 (TPH2), cocaine- and amphetamine-regulated transcript (CART), and 5-hydroxytryptamine (serotonin) receptor 2C (Htr2C)...
Research Interests:
ABSTRACTCore binding factor 1 (Cbfa1)/runt‐related transcription factor 2 (Runx2) has been identified as a “master gene” in osteoblastic differentiation. In this two‐part study, part I of the study was undertaken to test the hypothesis... more
ABSTRACTCore binding factor 1 (Cbfa1)/runt‐related transcription factor 2 (Runx2) has been identified as a “master gene” in osteoblastic differentiation. In this two‐part study, part I of the study was undertaken to test the hypothesis that bone regeneration is compromised in Cbfa1+/− mice. Compared with wild‐type mice, wound healing was dramatically delayed in Cbfa1+/− mice characterized by the presence of a small amount of bone near the base of the wounds. The bone defects were largely filled with fibrous connective tissues 3 weeks after surgery. Part II was performed to determine the effects of Cbfa1 in enhancing bone wound healing using a gene‐activated matrix (GAM) method. Cbfa1 cDNA was mixed with a biodegradable bovine type I collagen sponge and was inserted into the periodontal window wounds of mice. Control sponges were collagen matrix without Cbfa1 cDNA. Histological analysis and immunohistochemical staining demonstrated that compared with controls, there was increased new...
Research Interests:
Research Interests: Chemistry, Biomedical Engineering, Biology, Immunohistochemistry, Cell Biology, and 15 moreAdult Stem Cells, Medicine, In Situ Hybridization, Bone Regeneration, Cell line, Cell Differentiation, Mice, Animals, Osteoblast, Osteocalcin, Luciferase, Osteogenesis, Bone Marrow Cells, Biochemistry and cell biology, and Gene expression profiling
Research Interests: Chemistry, Biomedical Engineering, Tissue Engineering, Biology, Wound Healing, and 14 moreCell Biology, Transcription Factors, Medicine, Bone Regeneration, Mice, Animals, Skull, Osteoblast, Mesenchymal Stem Cell, Tissue, Osteogenesis, Transfection, Mesenchymal Stromal Cells, and Biochemistry and cell biology
Research Interests:
Dlx5 plays an important role in the embryonic development of mineralized tissues. We hypothesized that Dlx5 also functions in regulating post-natal bone formation in mice. To prove this hypothesis, we infected 5-day-old bone sialoprotein... more
Dlx5 plays an important role in the embryonic development of mineralized tissues. We hypothesized that Dlx5 also functions in regulating post-natal bone formation in mice. To prove this hypothesis, we infected 5-day-old bone sialoprotein (BSP)/avian retroviral receptor gene (TVA) transgenic mice with replication-competent retroviral vectors expressing wild-type Dlx5 (RCAS- Dlx5WT) and mutated Dlx5 at arginine (R) 31 of its homeodomain (RCAS- Dlx5RH). Immunohistochemistry indicated that RCAS- Dlx5WT increased BSP and osteopontin (OPN) expression, whereas it decreased that of osteocalcin (OC). RCAS- Dlx5RH mediated opposite effects. Semi-quantitative RT-PCR confirmed these results. Ex vivo overexpression of RCAS- Dlx5WT in BSP/TVA calvarial cells promoted, whereas that of RCAS- Dlx5RH inhibited, mineralized nodule formation as compared with that in control cells. Our results suggest that Dlx5 promotes expression of early markers of osteogenic differentiation and increases mineralizati...
Research Interests: Dentistry, Biology, Immunohistochemistry, Medicine, Mutation, and 15 moreMice, Animals, Dental, Osteoblast, Osteocalcin, Osteopontin, Phenotype, Embryonic Development, Arginine, Osteogenesis, Bone Formation, Bone and Bones, Gene Expression Regulation, Extracellular Matrix Proteins, and reverse transcriptase polymerase chain reaction
Cellular and molecular events in osseointegration at the dental implant surface remain largely unknown. We hypothesized that bone marrow stromal cells (BMSCs) participate in this process, and that osterix (Osx) promotes implant... more
Cellular and molecular events in osseointegration at the dental implant surface remain largely unknown. We hypothesized that bone marrow stromal cells (BMSCs) participate in this process, and that osterix (Osx) promotes implant osseointegration. To prove this hypothesis, we tracked double-labeled BMSCs in implantation sites created in nude mice transplanted with these cells. We also inserted implants into the femurs of our established transgenic mice after local administration of viruses encoding Osx, to determine the osteogenic effects of Osx. Immunohistochemical results demonstrated that BMSCs can recruit from peripheral circulation and participate in wound healing and osseointegration after implantation. Microcomputed tomography (microCT) analysis revealed an increased bone density at the bone-to-implant interface in the Osx group, and histomorphometric analysis indicated an elevated level of bone-to-implant contact in the Osx group. We concluded that exogenous BMSCs participate ...
Research Interests:
Research Interests:
Bone sialoprotein (BSP) is a major non‐collagenous protein in mineralizing connective tissues such as dentin, cementum and calcified cartilage tissues. As a member of the Small Integrin‐Binding Ligand, N‐linked Glycoprotein (SIBLING) gene... more
Bone sialoprotein (BSP) is a major non‐collagenous protein in mineralizing connective tissues such as dentin, cementum and calcified cartilage tissues. As a member of the Small Integrin‐Binding Ligand, N‐linked Glycoprotein (SIBLING) gene family of glycoproteins, BSP is involved in regulating hydroxyapatite crystal formation in bones and teeth, and has long been used as a marker gene for osteogenic differentiation. In the most recent decade, new discoveries in BSP gene expression and regulation, bone remodeling, bone metastasis, and bone tissue engineering have been achieved with the help of transgenic mice. In this review, we discuss these new discoveries obtained from the literatures and from our own laboratory, which were derived from the use of transgenic mouse mutants related to BSP gene or its promoter activity. J. Cell. Physiol. 220: 30–34, 2009. © 2009 Wiley‐Liss, Inc.
Research Interests:
Research Interests: Chemistry, Tissue Engineering, Cell Biology, Medicine, Bone Regeneration, and 15 moreCell Differentiation, Cellular, Humans, Mice, Animals, Male, Periodontal Ligament, Cellular Physiology, Medical Physiology, Cementum, DENTAL CEMENTUM, Gene Expression Regulation, Pluripotent Stem Cells, reverse transcriptase polymerase chain reaction, and Tissue Scaffolds
Runx2 has been identified as “a master gene” for the differentiation of osteoblasts and Runx2‐deficient mice has demonstrated a complete absence of mature osteoblast and ossification. To further characterize the Runx2 responsive elements... more
Runx2 has been identified as “a master gene” for the differentiation of osteoblasts and Runx2‐deficient mice has demonstrated a complete absence of mature osteoblast and ossification. To further characterize the Runx2 responsive elements within the bone sialoprotein (BSP) promoter and further investigate into the role of Runx2 haploinsufficiency in osteoblast differentiation, mBSP9.0Luc mice and mBSP4.8Luc mice were crossed with Runx2‐deficient mice respectively. Luciferase assay, micro CT scan, and histological analysis were performed using tissues isolated from mBSP9.0luc/Runx2+/− mice, mBSP4.8luc/Runx2+/− mice and their corresponding Runx2+/+ littermates. Alkaline phosphatase activity, mineralization assays and RT‐PCR analysis using calvarial osteoblasts isolated from these transgenic mice were also performed. Luciferase assay demonstrated an early increase in luciferase expression in mBSP9.0luc/Runx2+/− mice before the expression level of luciferase dramatically decreased and tu...
Research Interests: Molecular Biology, Biology, Medicine, Gene expression, Transgenic Mice, and 15 moreCell Differentiation, Cellular, Mice, Animals, Osteoblast, Cellular Physiology, Medical Physiology, Luciferase, Gene Dosage, Osteogenesis, Bone Formation, Osteoblasts, Gene Expression Regulation, reverse transcriptase polymerase chain reaction, and Expression pattern
The purpose of this study was to determine the effects of bone sialoprotein (BSP) overexpression in bone metabolism in vivo by using a homozygous transgenic mouse line that constitutively overexpresses mouse BSP cDNA driven by the... more
The purpose of this study was to determine the effects of bone sialoprotein (BSP) overexpression in bone metabolism in vivo by using a homozygous transgenic mouse line that constitutively overexpresses mouse BSP cDNA driven by the cytomegalovirus (CMV) promoter. CMV‐BSP transgenic (TG) mice and wildtype mice were weighed, and their length, BMD, and trabecular bone volume were measured. Serum levels of RANKL, osteocalcin, osteoprotegerin (OPG), TRACP5b, and PTH were determined. Bone histomorphometry, von Kossa staining, RT‐PCR analysis, Western blot, MTS assay, in vitro mineralization assay, and TRACP staining were also performed to delineate phenotypes of this transgenic mouse line. Compared with wildtype mice, adult TG mice exhibit mild dwarfism, lower values of BMD, and lower trabecular bone volume. TG mice serum contained increased calcium levels and decreased PTH levels, whereas the levels of phosphorus and magnesium were within normal limits. TG mice serum also exhibited lower ...
Research Interests: Engineering, Endocrinology, Chemistry, Biological Sciences, Cell Differentiation, and 15 moreInternal Medicine, Bone, Female, Animals, Male, Cytomegalovirus, Bone Density, Dwarfism, Isoenzymes, Bone Mineral Density, Biological markers, Bone and Bones, Bone Resorption, Acid Phosphatase, and Medical and Health Sciences
Research Interests: Engineering, MicroRNA, Biology, Cell Biology, Medicine, and 15 moreSignal Transduction, Biological Sciences, Cell line, Cell Differentiation, Mice, Bone, Animals, Osteoblast, microRNAs, Osteogenesis, Osteoblasts, Gene expression profiling, Down-Regulation, reverse transcriptase polymerase chain reaction, and Medical and Health Sciences
Research Interests: Chemistry, Cell Biology, Biological Chemistry, Medicine, Biological Sciences, and 15 moreCell line, Mice, Animals, OSTEOMALACIA, Osteocalcin, Proteins, Alkaline phosphatase, Phenotype, CHEMICAL SCIENCES, Rickets, Osteoblasts, Bone and Bones, Hypophosphatemia, Cell Membrane, and Medical and Health Sciences
Research Interests: Endocrinology, Chemistry, Medicine, Gene expression, Biological Sciences, and 15 moreInternal Medicine, Cartilage, Mice, Animals, Bone Density, Calcium Sensing Receptor, Bone marrow, Osteoblast, Phenotype, Bone Formation, Knockout Mice, Bone and Bones, Calcification, Growth Plate, and Medical and Health Sciences
Research Interests: Materials Science, Biomaterials, Cell Biology, Medicine, Multidisciplinary, and 15 moreBone Regeneration, Cell Differentiation, Silk, Mice, Animals, Skull, Osteoblast, Osteocalcin, Mouse Model, Bone Formation, Induced Pluripotent Stem Cells, Materials Testing, Biocompatible Materials, Nuclear Matrix, and Nude mice
Research Interests: Chemistry, Cell Biology, Medicine, Cell Differentiation, Mice, and 15 moreAnimals, Osteoblast, Osteocalcin, Differentiation, Osteopontin, Alkaline phosphatase, Osteogenesis, Bone Formation, Cell Proliferation, Lipoprotein a, Bone Marrow Cells, Biochemistry and cell biology, Bone marrow stromal cells, Lipoprotein Lipase, and Medical biochemistry and metabolomics
Research Interests:
Periodontitis is twice as prevalent in diabetics as in nondiabetics, and type 2 diabetes (T2D)–associated periodontitis is severe in many cases due to the altered and aberrant functions of bone cells in hyperglycemic conditions.... more
Periodontitis is twice as prevalent in diabetics as in nondiabetics, and type 2 diabetes (T2D)–associated periodontitis is severe in many cases due to the altered and aberrant functions of bone cells in hyperglycemic conditions. Therefore, developing an effective method to halt the disease process, as well as restore and regenerate lost alveolar bone to reserve the natural teeth in diabetics, is critically important. In the current study, we applied a newly discovered adiponectin receptor agonist AdipoRon (APR) in experimental periodontitis in diabetic animal models and demonstrated the underlying molecular mechanisms. We found that when APR systemically quenched the blood sugar level in diet-induced obesity (DIO) diabetic mice, it reduced osteoclast numbers and alveolar bone loss significantly due to APR’s inhibition on osteoclast differentiation shown in our in vitro studies. APR also decreased the production of proinflammatory molecules CC chemokine ligand 2 and interleukin 6 in ...
Research Interests:
Epigenetic regulation of gene expression is a central mechanism that governs cell stemness, determination, commitment, and differentiation. It has been recently found that PHF8, a major H4K20/H3K9 demethylase, plays a critical role in... more
Epigenetic regulation of gene expression is a central mechanism that governs cell stemness, determination, commitment, and differentiation. It has been recently found that PHF8, a major H4K20/H3K9 demethylase, plays a critical role in craniofacial and bone development. In this study, we hypothesize that PHF8 promotes osteoblastogenesis by epigenetically regulating the expression of a nuclear matrix protein, special AT-rich sequence-binding protein 2 (SATB2) that plays pivotal roles in skeletal patterning and osteoblast differentiation. Our results showed that expression levels of PHF8 and SATB2 in preosteoblasts and bone marrow stromal cells (BMSCs) increased simultaneously during osteogenic induction. Overexpressing PHF8 in these cells upregulated the expression of SATB2, Runx2 and osterix, and bone matrix proteins. Conversely, knockdown of PHF8 reduced the expression of those genes. Furthermore, ChIP assays confirmed that PHF8 specifically bound to the transcription start site (TS...
Research Interests:
Research Interests: Materials Science, Orthopedic Surgery, Biomaterials, Osseointegration, Titanium, and 15 moreImmunohistochemistry, Nanotechnology, Transcription Factors, Medicine, Multidisciplinary, Real-time RT-PCR, Transgenic Mice, Bone Regeneration, Mice, Animals, Transcription Factor, Bone Formation, Base Sequence, real time polymerase chain reaction, and Pharmacology and pharmaceutical sciences
BET proteins are a group of epigenetic regulators controlling transcription through reading acetylated histone tails and recruiting transcription complexes. They are considered as potential therapeutic targets in many distinct diseases. A... more
BET proteins are a group of epigenetic regulators controlling transcription through reading acetylated histone tails and recruiting transcription complexes. They are considered as potential therapeutic targets in many distinct diseases. A novel synthetic bromodomain and extraterminal domain (BET) inhibitor, JQ1, was proved to suppress oncogene transcription and inflammatory responses. The present study was aimed to investigate the effects of JQ1 on inflammatory response and bone destruction in experimental periodontitis. We found that JQ1 significantly suppressed lipopolysaccharide (LPS)-stimulated inflammatory cytokine transcription, including interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha (TNF-α), as well as receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclast markers, such as c-Fos, nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 (NFATc1), tartrate-resistant acid phosphatase (TRAP) and cathepsin K in vitro. JQ1 also ...
Research Interests:
OBJECTIVE In this study, we aimed to investigate the therapeutic potential of miR-335-5p lipidoid nanocomplexes coated on Titanium (Ti) SLActive surface by lyophilization. DESIGN In our model, we coated miR-335-5p/Lipidoid nanoparticles... more
OBJECTIVE In this study, we aimed to investigate the therapeutic potential of miR-335-5p lipidoid nanocomplexes coated on Titanium (Ti) SLActive surface by lyophilization. DESIGN In our model, we coated miR-335-5p/Lipidoid nanoparticles on titanium implant, seeded GFP-labelled mouse bone marrow stromal cells (BMSCs) onto the functionalized Ti implant surface, and analyzed the transfection efficiency, cell adhesion, proliferation, and osteogenic activity of the bone-implant interface. RESULTS The Ti SLActive surface displayed a suitable hydrophilicity ability and provided a large surface area for miRNA loading, enabling spatial retention of the miRNAs within the nanopores until cellular delivery. We demonstrated a high transfection efficiency of miR-335-5p lipidoid nanoparticles in BMSCs seeded onto the Ti SLActive surface, even after 14 days. Alkaline phosphatase (ALP) activity and cell vitality were significantly increased in BMSCs transfected with miR-335-5p at 7 and 14 days as opposed to cells transfected with negative controls. When miR-335-5p transfected BMSCs were induced to undergo osteogenic differentiation, we detected increased mRNA expression of osteogenic markers including Alkaline phosphatase (ALP), collagen I (COL1), osteocalcin (OCN) and bone sialoprotein (BSP) at 7 and 14 days as compared with negative controls. CONCLUSION MiR-335-5p lipidoid nanoparticles could be used as a new cost-effective methodology to increase the osteogenic capacity of biomedical Ti implants.