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1.
The emerging role of extracellular Ca2+ in osteo/odontogenic differentiation and the involvement of intracellular Ca 2+ signaling: From osteoblastic cells to dental pulp cells and odontoblasts.
An, S
Journal of cellular physiology. 2019;(3):2169-2193
Abstract
Calcium ions (Ca2+ ) is the main element of dental pulp capping materials. Ca 2+ signaling plays a crucial role in a myriad of cell activities. An overwhelming array of studies have already reported the experimental and clinical benefits of Ca2+ -enriched materials in the treatment of teeth with accidental vital pulp exposure and incomplete root formation. Thus, Ca2+ signaling has always been an excellent target for the design of various novel biomaterials for use in revitalizing or regenerative endodontic procedures. However, the molecular mechanisms that enable dental pulp cells (DPCs) to detect and respond to extracellular Ca2+ have not been characterized in detail before. In this review, we mainly outline the pathways by which the cell detects and responds to extracellular Ca2+ , as well as the relevant regulatory paths in DPCs and odontoblasts, and discuss the potential role of Ca2+ as a therapeutic tool. Moreover, because DPCs share many of the same functional properties that are found in osteoblasts, some comparisons with bone cells were additionally incorporated into this text.
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2.
Cajanine promotes osteogenic differentiation and proliferation of human bone marrow mesenchymal stem cells.
Zhao, ZY, Yang, L, Mu, X, Xu, L, Yu, X, Jiao, Y, Zhang, X, Fu, L
Advances in clinical and experimental medicine : official organ Wroclaw Medical University. 2019;(1):45-50
Abstract
BACKGROUND Seed cells - mesenchymal stem cells (MSCs) - appear to be an attractive tool in the context of tissue engineering. Bone marrow represents the main source of MSCs for both experimental and clinical studies. However, the number limitation of bone marrow MSCs (BMSCs) and decreased function caused by proliferation make the search for adequate alternative sources of these cells for autologous and allogenic transplant necessary. OBJECTIVES This study was aimed to investigate the roles of cajanine isolated from the extracts of Cajanus cajan L. Millsp. in the proliferation and differentiation of BMSCs, and to discover the mechanism of proliferation of BMSCs promoted by cajanine. MATERIAL AND METHODS Bone marrow mesenchymal stem cells were cultured in high-glucose Dulbecco's Modified Eagle's Medium (DMEM) and osteogenic differentiation was induced by adding dexamethasone, ascorbic acid and β-glycerophosphate supplements. Bone marrow MSCs were cultured in medium without cajanine or supplemented with cajanine. The information about the proliferation and osteogenic differentiation of BMSCs was collated. The osteogenic differentiation potential of BMSCs was also assessed at the 3rd passage by Von Kossa staining. To observe cell signal transduction changes of BMSCs after culturing them with cajanine for 24 h, the western blot analysis was performed to detect phosphorylated cell cycle proteins and activated cyclins. RESULTS After osteogenic induction, the differentiation of BMSCs was accelerated by cajanine treatment. Osteogenesis markers were upregulated by cajanine treatment at both protein and mRNA levels. Cajanine obviously promoted the proliferation of BMSCs. After BMSCs were cultured with cajanine for 24 h, the cell cycle regulator proteins were phosphorylated or upregulated. CONCLUSIONS Cajanine can promote the expansion efficiency of BMSCs, at the same time keeping their multi-differentiation potential. Cajanine can activate the cell cycle signal transduction pathway, thus inducing cells to enter the G1/S phase and accelerating cells entering the G2/M phase. This study can contribute to the development of cajanine-based drugs in tissue engineering.
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3.
The diurnal variation of bone formation is attenuated in adult patients with type 2 diabetes.
Hygum, K, Starup-Linde, J, Harsløf, T, Jørgensen, NR, Hartmann, B, Holst, JJ, Langdahl, BL
European journal of endocrinology. 2019;(3):221-231
Abstract
OBJECTIVE Bone turnover has a diurnal variation influenced by food intake, incretin hormones, the sympathetic nervous system and osteocyte function. The aim of the study was to compare diurnal variation in bone turnover in patients with diabetes and controls. DESIGN A clinical 24-h study with patients with type 1 diabetes (n = 5), patients with type 2 diabetes (n = 5) and controls (n = 5). METHODS Inclusion criterion: age >50 years. Exclusion criteria: diseases/medication that affect bone metabolism or recent use of incretin-based drugs. We drew blood samples hourly during the day and every 3 h during the night. We served an identical diet on all study days. We used repeated-measures one-way ANOVA to compare the levels of the investigated markers, and we quantified the effect of time by comparing group mean standard deviations. RESULTS The bone formation marker procollagen type 1 N-terminal propeptide showed a significant interaction between time and group (P = 0.01), and the mean standard deviation was lower in patients with type 2 diabetes compared with controls (P = 0.04) and patients with type 1 diabetes (P = 0.02). Other markers of bone formation and resorption showed significant effect of time. Levels of glucagon-like peptide-2, glucose-dependent insulinotropic peptide and sclerostin only showed significant effect of time (all P values 0.01), but levels of sclerostin tended to being highest in type 2 diabetes and lowest in controls. CONCLUSIONS The diurnal variation in bone formation is attenuated in patients with type 2 diabetes. This is not explained by changes in incretin hormone levels, but possibly mediated by sclerostin.
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4.
Biological Properties of Calcium Phosphate Bioactive Glass Composite Bone Substitutes: Current Experimental Evidence.
Karadjian, M, Essers, C, Tsitlakidis, S, Reible, B, Moghaddam, A, Boccaccini, AR, Westhauser, F
International journal of molecular sciences. 2019;(2)
Abstract
Standard treatment for bone defects is the biological reconstruction using autologous bone-a therapeutical approach that suffers from limitations such as the restricted amount of bone available for harvesting and the necessity for an additional intervention that is potentially followed by donor-site complications. Therefore, synthetic bone substitutes have been developed in order to reduce or even replace the usage of autologous bone as grafting material. This structured review focuses on the question whether calcium phosphates (CaPs) and bioactive glasses (BGs), both established bone substitute materials, show improved properties when combined in CaP/BG composites. It therefore summarizes the most recent experimental data in order to provide a better understanding of the biological properties in general and the osteogenic properties in particular of CaP/BG composite bone substitute materials. As a result, BGs seem to be beneficial for the osteogenic differentiation of precursor cell populations in-vitro when added to CaPs. Furthermore, the presence of BG supports integration of CaP/BG composites into bone in-vivo and enhances bone formation under certain circumstances.
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5.
Immobilization of Denosumab on Titanium Affects Osteoclastogenesis of Human Peripheral Blood Monocytes.
Beck, F, Hartmann, ES, Koehler, MI, Redeker, JI, Schluessel, S, Schmitt, B, Fottner, A, Unger, M, van Griensven, M, Michael, J, et al
International journal of molecular sciences. 2019;(5)
Abstract
Immobilization of proteins has been examined to improve implant surfaces. In this study, titanium surfaces were modified with nanofunctionalized denosumab (cDMAB), a human monoclonal anti-RANKL IgG. Noncoding DNA oligonucleotides (ODN) served as linker molecules between titanium and DMAB. Binding and release experiments demonstrated a high binding capacity of cDMAB and continuous release. Human peripheral mononuclear blood cells (PBMCs) were cultured in the presence of RANKL/MCSF for 28 days and differentiated into osteoclasts. Adding soluble DMAB to the medium inhibited osteoclast differentiation. On nanofunctionalized titanium specimens, the osteoclast-specific TRAP5b protein was monitored and showed a significantly decreased amount on cDMAB-titanium in PBMCs + RANKL/MCSF. PBMCs on cDMAB-titanium also changed SEM cell morphology. In conclusion, the results indicate that cDMAB reduces osteoclast formation and has the potential to reduce osteoclastogenesis on titanium surfaces.
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6.
Osteointegration of a Biocomposite Suture Anchor After Arthroscopic Shoulder Labral Repair.
Sugaya, H, Suzuki, K, Yoshimura, H, Tanaka, M, Yamazaki, T, Watanabe, M, Iwaso, H, Inaoka, T, Sugimoto, H, Matsuki, K, et al
Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association. 2019;(12):3173-3178
Abstract
PURPOSE To evaluate osteoconductivity of a poly-L-lactide co-glycolide (PLG)-calcium sulfate (CS)-β-tricalcium phosphate (β-TCP) biocomposite suture anchor after arthroscopic shoulder labral repair. METHODS The subjects of this study were patients who participated in a clinical trial for acquisition of marketing approval of a PLG-CS-β-TCP biocomposite anchor in Japan. They underwent arthroscopic labral repair using the anchor, and computed tomographic (CT) images of the glenoid were obtained 2 years after surgery. Osteoconductivity at the anchor sites was evaluated with the CT images using the established ossification quality score. Shoulder function scores including the Rowe score and Japanese Shoulder Society shoulder instability score were also assessed 2 years after surgery. RESULTS CT images and functional scores were obtained from 37 patients, comprising 29 men and 8 women with a mean age of 29 years (range, 25-33 years) at surgery. A total of 148 anchors were implanted in the 37 shoulders. Osteoconductivity was seen in 133 of 148 anchor sites (90.0%) 2 years after implantation. No significant differences in osteoconductivity were found by anchor diameter or position. The Rowe score significantly improved from 39.9 points (95% confidence interval [CI], 33.8-45.9 points) preoperatively to 96.6 points (95% CI, 95.1-98.1 points) at 2 years postoperatively (P < .001). The Japanese Shoulder Society shoulder instability score also significantly improved, from 63.1 points (95% CI, 58.4-67.7 points) preoperatively to 96.3 points (95% CI, 94.7-97.8 points) at 2 years postoperatively (P < .001). CONCLUSIONS Biocomposite suture anchors made of PLG, CS, and β-TCP exhibited some osteoconductivity 2 years after arthroscopic labral repair, as well as good clinical outcomes. LEVEL OF EVIDENCE Level IV, therapeutic case series.
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Effect of Daily Exposure to an Isolated Soy Protein Supplement on Body Composition, Energy and Macronutrient Intake, Bone Formation Markers, and Lipid Profile in Children in Colombia.
Mejía, W, Córdoba, D, Durán, P, Chacón, Y, Rosselli, D
Journal of dietary supplements. 2019;(1):1-13
Abstract
A soy protein-based supplement may optimize bone health, support physical growth, and stimulate bone formation. This study aimed to assess the effect of a daily soy protein supplement (SPS) on nutritional status, bone formation markers, lipid profile, and daily energy and macronutrient intake in children. One hundred seven participants (62 girls), ages 2 to 9, started the study and were randomly assigned to lunch fruit juice with (n = 57, intervention group) or without (n = 50, control group) addition of 45 g (230 Kcal) of a commercial SPS during 12 months; 84 children (51 girls, 33 boys) completed the study (45 and 39 intervention and control, respectively). Nutritional assessment included anthropometry and nutrient intakes; initial and final blood samples were taken; insulin-like growth factor-I (IGF-I), osteocalcin, bone specific alkaline phosphatase (BAP), insulin-like growth factor binding protein-3 (IGFBP-3), cholesterol, triglycerides, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) were analyzed. Statistically significant changes (p < .05) in body mass index and weight for age Z scores were observed between groups while changes in body composition were not. Changes in energy, total protein, and carbohydrate intakes were significantly higher in the intervention group (p < .01). Calorie intake changes were statistically significant between groups (p < .001), and BAP decreased in both groups, with values within normal ranges. Osteocalcin, IGFBP-3, and lipid profile were not different between groups. IGF-I levels and IGF/IGFBP-3 ratio increased significantly in both groups. In conclusion, changes in macronutrient and energy intake and nutritional status in the intervention group compared to control group may ensure harmonious and adequate bone health and development.
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8.
The Emerging Role of Glucose Metabolism in Cartilage Development.
Hollander, JM, Zeng, L
Current osteoporosis reports. 2019;(2):59-69
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Abstract
PURPOSE OF REVIEW Proper cartilage development is critical to bone formation during endochondral ossification. This review highlights the current understanding of various aspects of glucose metabolism in chondrocytes during cartilage development. RECENT FINDINGS Recent studies indicate that chondrocytes transdifferentiate into osteoblasts and bone marrow stromal cells during endochondral ossification. In cartilage development, signaling molecules, including IGF2 and BMP2, tightly control glucose uptake and utilization in a stage-specific manner. Perturbation of glucose metabolism alters the course of chondrocyte maturation, suggesting a key role for glucose metabolism during endochondral ossification. During prenatal and postnatal growth, chondrocytes experience bursts of nutrient availability and energy expenditure, which demand sophisticated control of the glucose-dependent processes of cartilage matrix production, cell proliferation, and hypertrophy. Investigating the regulation of glucose metabolism may therefore lead to a unifying mechanism for signaling events in cartilage development and provide insight into causes of skeletal growth abnormalities.
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ZNF521 Represses Osteoblastic Differentiation in Human Adipose-Derived Stem Cells.
Chiarella, E, Aloisio, A, Scicchitano, S, Lucchino, V, Montalcini, Y, Galasso, O, Greco, M, Gasparini, G, Mesuraca, M, Bond, HM, et al
International journal of molecular sciences. 2018;(12)
Abstract
Human adipose-derived stem cells (hADSCs) are multipotent mesenchymal cells that can differentiate into adipocytes, chondrocytes, and osteocytes. During osteoblastogenesis, the osteoprogenitor cells differentiate into mature osteoblasts and synthesize bone matrix components. Zinc finger protein 521 (ZNF521/Zfp521) is a transcription co-factor implicated in the regulation of hematopoietic, neural, and mesenchymal stem cells, where it has been shown to inhibit adipogenic differentiation. The present study is aimed at determining the effects of ZNF521 on the osteoblastic differentiation of hADSCs to clarify whether it can influence their osteogenic commitment. The enforced expression or silencing of ZNF521 in hADSCs was achieved by lentiviral vector transduction. Cells were cultured in a commercial osteogenic medium for up to 20 days. The ZNF521 enforced expression significantly reduced osteoblast development as assessed by the morphological and molecular criteria, resulting in reduced levels of collagen I, alkaline phosphatase, osterix, osteopontin, and calcium deposits. Conversely, ZNF521 silencing, in response to osteoblastic stimuli, induced a significant increase in early molecular markers of osteogenesis and, at later stages, a remarkable enhancement of matrix mineralization. Together with our previous findings, these results show that ZNF521 inhibits both adipocytic and osteoblastic maturation in hADSCs and suggest that its expression may contribute to maintaining the immature properties of hADSCs.
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Bone metabolic responses to low energy availability achieved by diet or exercise in active eumenorrheic women.
Papageorgiou, M, Martin, D, Colgan, H, Cooper, S, Greeves, JP, Tang, JCY, Fraser, WD, Elliott-Sale, KJ, Sale, C
Bone. 2018;:181-188
Abstract
PURPOSE We aimed to explore the effects of low energy availability (EA)[15 kcal·kg lean body mass (LBM)-1·d-1] achieved by diet or exercise on bone turnover markers in active, eumenorrheic women. METHODS By using a crossover design, ten eumenorrheic women (VO2 peak: 48.1 ± 3.3 ml·kg-1·min-1) completed all three, 3-day conditions in a randomised order: controlled EA (CON; 45 kcal·kgLBM-1·d-1), low EA through dietary energy restriction (D-RES; 15 kcal·kgLBM-1·d-1) and low EA through increasing exercise energy expenditure (E-RES; 15 kcal·kgLBM-1·d-1), during the follicular phase of three menstrual cycles. In CON, D-RES and E-RES, participants consumed diets providing 45, 15 and 45 kcal·kgLBM-1·d-1. In E-RES only, participants completed supervised running sessions (129 ± 10 min·d-1) at 70% of their VO2 peak that resulted in an exercise energy expenditure of 30 kcal·kg LBM-1·d-1. Blood samples were collected at baseline (BASE) and at the end of the 3-day period (D6) and analysed for bone turnover markers (β-CTX and P1NP), markers of calcium metabolism (PTH, albumin-adjusted Ca, Mg and PO4) and hormones (IGF-1, T3, insulin, leptin and 17β-oestradiol). RESULTS In D-RES, P1NP concentrations at D6 decreased by 17% (BASE: 54.8 ± 12.7 μg·L-1, D6: 45.2 ± 9.3 μg·L-1, P < 0.001, d = 0.91) and were lower than D6 concentrations in CON (D6: 52.5 ± 11.9 μg·L-1, P = 0.001). P1NP did not change significantly in E-RES (BASE: 55.3 ± 14.4 μg·L-1, D6: 50.9 ± 15.8 μg·L-1, P = 0.14). β-CTX concentrations did not change following D-RES (BASE: 0.48 ± 0.18 μg·L-1, D6: 0.55 ± 0.17 μg·L-1) or E-RES (BASE: 0.47 ± 0.24 μg·L-1, D6: 0.49 ± 0.18 μg·L-1) (condition × time interaction effect, P = 0.17). There were no significant differences in P1NP (P = 0.25) or β-CTX (P = 0.13) responses between D-RES and E-RES. Both conditions resulted in reductions in IGF-1 (-13% and - 23% from BASE in D-RES and E-RES, both P < 0.01) and leptin (-59% and - 61% from BASE in D-RES and E-RES, both P < 0.001); T3 decreased in D-RES only (-15% from BASE, P = 0.002) and PO4 concentrations decreased in E-RES only (-9%, P = 0.03). CONCLUSIONS Low EA achieved through dietary energy restriction resulted in a significant decrease in bone formation but no change in bone resorption, whereas low EA achieved through exercise energy expenditure did not significantly influence bone metabolism. Both low EA conditions elicited significant and similar changes in hormone concentrations.