cyclin-d1 and Osteoporosis

Osteoporosis is a systemic disorder of bone metabolism. This study aimed to investigate the impacts and possible mechanisms of Arctiin, a lignin isolated from

Topics: Animals; Cyclin D1; Furans; Glucosides; Mice; Osteoblasts; Osteogenesis; Osteoporosis

MiRNAs have gained tremendous attention as studies have shown that miRNAs play important roles in osteoporosis (OP) progression. This study attempted to explore whether miR-23b-3p is involved in the pathogenesis of OP. We detected the miR-23b-3p and Cyclin D1 (CCND1) expressional patterns in the bone of patients with or without OP relying on the GEO database. β-Glycerophosphate disodium salt and L-ascorbic acid were utilized to stimulate differentiation of MC3T3-E1 cells. Cell proliferative, apoptotic abilities, and cell cycle distribution were determined by CCK-8 and flow cytometry experiments. TargetScan and dual-luciferase reporter analysis were employed to predict and verify the targets of miR-23b-3p. Western blot was implemented to detect the expression of CCND1, apoptosis-related proteins, and cell osteogenesis-related proteins. ALP activity of MC3T3-E1 cells was measured using ALP kit. MiR-23b-3p was increased in OP specimens. Gain-/loss-of-function analysis indicated that the miR-23b-3p inhibited proliferation and differentiation and promoted apoptosis of MC3T3-E1 cells. The levels of Bax and cleaved caspase-3 were increased while those of Bcl-2 were decreased. ALP activity was reduced, and the levels of ALP, Runx2, Osterix, and OPN were declined in MC3T3-E1 cells relative to control. Further analyses demonstrated that CCND1 was a putative target gene of miR-23b-3p. Moreover, knockdown of CCND1 could reverse the impacts of miR-23b-3p inhibitor in MC3T3-E1 cells. MiR-23b-3p functioned as an O-positive factor through regulating cell cycle, proliferation, apoptosis, and differentiation via targeting CCND1.

Topics: Animals; Apoptosis; Base Sequence; Cell Cycle; Cell Differentiation; Cell Line; Cell Proliferation; Cyclin D1; Disease Progression; Gene Expression Regulation; Humans; Mice; MicroRNAs; Osteoporosis; RNA, Small Interfering

Topics: 3T3 Cells; Animals; Bone and Bones; Bone Density Conservation Agents; Calcification, Physiologic; Cyclin D1; Databases, Factual; Extracellular Matrix; Flavanones; Forkhead Box Protein O1; Glucocorticoids; Humans; Mice; Osteoporosis; Proto-Oncogene Proteins c-akt; PTEN Phosphohydrolase; Signal Transduction; TOR Serine-Threonine Kinases

Imbalances in bone formation and resorption cause osteoporosis. Mounting evidence supports that brain-derived neurotrophic factor (BDNF) implicates in this process. 7,8-Dihydroxyflavone (7,8-DHF), a plant-derived small molecular TrkB agonist, mimics the functions of BDNF. We show that both BDNF and 7,8-DHF promoted the proliferation, osteogenic differentiation, and mineralization of MC3T3-E1 cells. These effects might be attributed to the activation of the Wnt/β-catenin signaling pathway as the expression of cyclin D1, phosphorylated-glycogen synthase kinase-3β (p-GSK3β), β-catenin, Runx2, Osterix, and osteoprotegerin (OPG) was all significantly up-regulated. Knockdown of β-catenin restrained the up-regulation of Runx2 and Osterix stimulated by 7,8-DHF. In particular, blocking TrkB by its specific inhibitor K252a suppressed 7,8-DHF-induced osteoblastic proliferation, differentiation, and expression of osteoblastogenic genes. Moreover, BDNF and 7,8-DHF repressed osteoclastic differentiation of RAW264.7 cells. The transcription factor c-fos and osteoclastic genes such as tartrate-resistant acid phosphatase (TRAP), matrix metalloprotein-9 (MMP-9), Adamts5 were inhibited by 7,8-DHF. More importantly, 7,8-DHF attenuated bone loss, improved trabecular microarchitecture, tibial biomechanical properties, and bone biochemical indexes in an ovariectomy (OVX) rat model. The current work highlights the dual regulatory effects that 7,8-DHF exerts on bone remodeling.

Topics: Animals; beta Catenin; Bone and Bones; Bone Remodeling; Cell Differentiation; Cell Proliferation; Core Binding Factor Alpha 1 Subunit; Cyclin D1; Disease Models, Animal; Female; Flavones; Osteoblasts; Osteoclasts; Osteogenesis; Osteoporosis; Osteoprotegerin; Ovariectomy; Rats; Sp7 Transcription Factor; Wnt Signaling Pathway

Epigallocatechin‑3‑gallate (EGCG) is a polyphenolic compound extracted and isolated from green tea, which has a variety of important biological activities in vitro and in vivo, including anti‑tumor, anti‑oxidation, anti‑inflammation and lowering blood pressure. The aim of the present study was to investigate the protective effect of EGCG against secondary osteoporosis in a mouse model via the Wnt/β‑catenin signaling pathway. Reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and western blotting were used to analyze runt‑related transcription factor 2 and osterix mRNA expression, and the protein expression of cyclin D1, Wnt and β‑catenin, and suppressed peroxisome proliferator‑activated receptor γ protein expression. The protective effect of EGCG against secondary osteoporosis was examined and its potential mechanism was analyzed. Treatment with EGCG significantly decreased serum calcium, urinary calcium, body weight and body fat, and increased leptin levels in mice with secondary osteoporosis. In addition, EGCG treatment significantly inhibited the structure score of articular cartilage and cancellous bone in proximal tibia metaphysis in mice with secondary osteoporosis. Treatment also significantly decreased alkaline phosphatase activity, runt‑related transcription factor 2 and osterix mRNA expression. EGCG also significantly induced the protein expression of cyclin D1, Wnt and β‑catenin, and suppressed peroxisome proliferator‑activated receptor γ protein expression in mice with secondary osteoporosis. Taken together, these results suggest that EGCG may be a possible new drug in clinical settings.

Topics: Animals; beta Catenin; Calcium; Cartilage; Catechin; Cell Proliferation; Cyclin D1; Disease Models, Animal; Humans; Mice; Osteoporosis; PPAR gamma; Tea; Wnt Signaling Pathway

Curculigoside, a phenolic glycoside, is the main active compound of Curculigo orchioides (Amaryllidaceae, rhizome). C. orchioides is a traditional Chinese herbal medicine and has been commonly used to treat orthopedic disorders and bone healing in Asia. This study evaluated the effect of curculigoside on osteogenic differentiation of human amniotic fluid-derived stem cells (hAFSCs). The results showed that curculigoside stimulated alkaline phosphatase activity and calcium deposition of hAFSCs during osteogenic differentiation in a dose-dependent manner (1-100 μg/mL), while the effects were reduced at the higher concentration of 200 μg/mL. From reverse transcriptase-polymerase chain reaction analysis, the osteogenic genes osteopontin (OPN) and Collagen I were upregulated with curculigoside treatment (1-100 μg/mL). Concurrently, the ratio of osteoprotegerin (OPG) to receptor activator of nuclear factor kappa-B ligand (RANKL) was increased, indicating the inhibition of osteoclastogenesis by curculigoside. Moreover, the role of Wnt/β-catenin signaling during curculigoside treatment was revealed by the upregulation of β-catenin and Cyclin D1. In summary, curculigoside improved osteogenesis and inhibited osteoclastogenesis of hAFSCs, suggesting its potential use to regulate hAFSC osteogenic differentiation for treating bone disorders.

Topics: Alkaline Phosphatase; Amniotic Fluid; Benzoates; beta Catenin; Calcium; Cell Differentiation; Cell Proliferation; Cells, Cultured; Collagen; Curculigo; Cyclin D1; Glucosides; Humans; Medicine, Chinese Traditional; Osteoclasts; Osteogenesis; Osteopontin; Osteoporosis; Osteoprotegerin; RANK Ligand; Stem Cells; Up-Regulation; Wnt Signaling Pathway

The bone-resorbing osteoclast is essential for skeletal remodeling, yet its deregulation contributes to diseases such as osteoporosis and cancer bone metastasis. Here we identify histone deacetylase 7 (HDAC7) as a key negative regulator of osteoclastogenesis and bone resorption using both in vitro cellular and molecular analyses and in vivo characterization of conditional HDAC7-knockout mice. Bone marrow osteoclast differentiation assays reveal that HDAC7 overexpression suppresses, whereas HDAC7 deletion enhances, osteoclastogenesis. Mechanistically, in the absence of receptor activator of nuclear factor κ-B ligand (RANKL), HDAC7 attenuates β-catenin function and cyclin D1 expression, thereby reducing precursor proliferation; upon RANKL activation, HDAC7 suppresses NFATc1 and prevents β-catenin down-regulation, thereby blocking osteoclast differentiation. Consequently, HDAC7 deletion in the osteoclast lineage results in a 26% reduction in bone mass (P = 0.003) owing to 102% elevated bone resorption (P = 0.01). These findings are clinically significant in light of the remarkable therapeutic potentials of HDAC inhibitors for several diseases such as cancer, diabetes, and neurodegeneration.

Topics: Animals; beta Catenin; Bone and Bones; Bone Density; Bone Remodeling; Bone Resorption; Cell Differentiation; Cell Line; Cell Proliferation; Cyclin D1; Down-Regulation; Histone Deacetylases; Mice; Mice, Knockout; NFATC Transcription Factors; Osteoclasts; Osteoporosis; RANK Ligand

Functional analysis in mice has established an absolute requirement of JunB, a member of the AP-1 transcription factor family, during early embryonic development. To investigate the role of JunB during mid and late gestation and postnatally Ubi-junB transgenic mice were used to generate two junB-/- Ubi-junB mutant lines, in which embryonic lethality was rescued but strongly reduced JunB expression in several adult tissues was observed. Mutant mice from both rescue lines were growth retarded and shared significantly reduced longitudinal bone growth. Mutant long bones were characterised by reduced numbers of growth plate chondrocytes and a severe osteoporosis. Decreased JunB levels in epiphysal growth plate chondrocytes and bone lining osteoblasts correlated with deregulated expression of Cyclin A, Cyclin D1 and p16INK4a, key regulators of cell cycle control. Furthermore, junB-/- Ubi-junB bone marrow stromal cells were unable to differentiate into bone forming osteoblasts in vitro. Our data demonstrate that JunB plays a crucial role in endochondral ossification by regulating proliferation and function of chondrocytes and osteoblasts.

Topics: Animals; Bone Development; Chondrocytes; Cyclin A; Cyclin D1; Cyclin-Dependent Kinase Inhibitor p16; Immunohistochemistry; In Situ Hybridization; Mice; Mice, Knockout; Mutation; Osteoblasts; Osteoporosis; Proto-Oncogene Proteins c-jun; Reverse Transcriptase Polymerase Chain Reaction