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Can we accelerate the osteoporotic bone fracture healing response?
Published in Peter V. Giannoudis, Thomas A. Einhorn, Surgical and Medical Treatment of Osteoporosis, 2020
Martijn van Griensven, Elizabeth Rosado Balmayor
In a preliminary in vitro study for bone regeneration in an osteoporotic setting, we could show that transfecting osteoporotic osteoblasts using lipofectamine and antagomir for miR-100 was able to restore the transcription of BMP-R2. Thereby, osteoanabolic signals could be transferred again into the osteoblasts that started to produce collagen Iα1 as a typical protein of the bone extracellular matrix. Moreover, the osteoblasts increase the production of alkaline phosphatase and osteocalcin. Using an antagomir against miR-148a increased MAFB (V-maf musculoaponeurotic fibrosarcoma oncogene homolog B) and thereby inhibited the maturation of osteoclasts. This resulted in less resorptive activity.
The Role of the Macrophage in Immunity
Published in Richard C. Niemtzow, Transmembrane Potentials and Characteristics of Immune and Tumor Cell, 2020
Macrophage activating factor binds to the macrophages via a carbohydrate moiety on the surface of the cell.50 It appears that the essential carbohydrate in the receptor for MAF is D-mannose. In humans and guinea pigs, the essential carbohydrate moiety in the MIF receptor is L-fucose.45 Sialic acid may also play a role in the interaction of MAF with its receptor.50 The fact that MAF and MIF seem to be blocked by different carbohydrates supports the concept that they are separate molecules. However, it could be possible that there are two receptors on a single cell for the same molecule, one containing the sugar D-mannose and leading to macrophage activation, the other containing L-fucose and leading to migration inhibition.
Genetic Control of Macrophage Antitumor Responses
Published in Gloria H. Heppner, Amy M. Fulton, Macrophages and Cancer, 2019
Mary M. Stevenson, Emil Skamene
Recently, liposome-encapsulated macrophage-activating agents (lymphokine preparations containing MAF, γ-IFN and muramyl dipeptide (MDP), and its various lipophilic derivatives) have been demonstrated to activate murine macrophage tumoricidal activity in vitro.123 The in vitro activation of macrophages by liposome-encapsulated macrophage-activating agents was, furthermore, demonstrated to correlate with the activation in vivo by liposomes containing the immunomodulators of host macrophages, resulting in destruction of metastases.124 Systemic administration of immunomodulators such as MAF or MDP is ineffective due to the short half-life of these substances in the host. However, encapsulation in liposomes results in this therapy being effective because the immunomodulators are triggered to the target cell, that is, the macrophage. It has been demonstrated that 80 to 90% of liposomes are taken up by the mononuclear phagocytes of the liver, spleen, lung, lymph nodes, bone marrow, and peripheral blood.125
LDB1-mediated transcriptional complexes are sensitive to islet stress
Published in Islets, 2022
Yanping Liu, Jessica D. Kepple, Anath Shalev, Chad S. Hunter
The insulin-producing β-cell, tasked with mediating glucose homeostasis via glucose-stimulated insulin secretion (GSIS), is central to the etiology of type 1 (T1D, loss of pancreatic β-cells) or type 2 diabetes (T2D, reduced functional β-cell mass).1–4 β-cells are exquisitely tuned to the milieu of external stimuli to modulate insulin expression, production, maturation, and secretion. While acute elevations in plasma glucose levels impart stimulatory effects of increased Insulin gene transcription and hormone secretion, prolonged supraphysiological glucose treatment in cell lines or in vivo (i.e., glucotoxicity) reduces β-cell function and viability. These effects are mediated, in part, by changes in levels and/or function of various islet transcription factors (TF). One example is the TF MAFA, which is sensitive to changes in nutrients and cytokines. MAFA expression and function is required for Insulin transcription and is induced by acute glucose treatment.5–9 However, β-cell stresses imparted by prolonged in vitro incubation with high glucose, fatty acids, or proinflammatory cytokines (e.g., TNFα, IFNγ, Interleukin-1β (IL-1β);10–12), as well as in vivo diabetic mouse models (e.g., db/db,13,14), leads to MAFA inactivation and loss, likely stimulating a cascade of β-cell dysfunction.15
Cross talk between exosomes and pancreatic β-cells in diabetes
Published in Archives of Physiology and Biochemistry, 2022
One of the major developments in lncRNAs over the past several years is that lncRNAs exist in various body fluids, such as serum (Shen et al.2017), plasma (Tan et al.2016), and urine (Terracciano et al.2017). Circulating lncRNAs could target distant cells or organs and perform a regulatory function in a new location through exosomes. β-cell-derived lncRNAs in the circulation can restore insulin synthesis and increase the number of pancreatic β-cells. PDX-1 and MafA are key proteins for insulin secretion regulation (Guo et al.2012). GLUT2 is a glucose transporter essential for activating glucose-sensitive genes (Thorens 2015). Microarray technology indicated that the circulating level of lncRNA-p3134 in T2D patients was higher than in non-diabetic controls. Further research in MIN6 cells and isolated mouse islet cells shows β cell-derived lncRNA-p3134 regulating the expression of PDX-1, MafA, and transcription factor 7-like 2, thereby enhancing GSIS (Figure 3⑤). Furthermore, when the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signals were blocked by specific inhibitor, lncRNA-p3134-mediated insulin secretion decreased (Ruan et al.2018) (Figure 3⑤). Simulation of the PI3K/AKT pathway phosphorylates the mammalian target of rapamycin (mTOR), governing promoting cell proliferation (Ruan et al.2018). In summary, circulating lncRNA-p3134 maintains insulin levels through regulating both insulin section and β-cell mass.
LncRNA TUG1 positively regulates osteoclast differentiation by targeting v-maf musculoaponeurotic fibrosarcoma oncogene homolog B
Published in Autoimmunity, 2020
Ya-jing Du, Qiong-qiong Yu, Xiao-fei Zheng, Su-ping Wang
V‐maf musculoaponeurotic fibrosarcoma oncogene homolog B (MafB) is a member of the Maf family and expressed selectively in monocytes and macrophages [6]. Kim et al. [7] revealed that MafB negatively regulated receptor activator of nuclear factor κB ligand (RANKL)-mediated osteoclast differentiation via repressing the expressions of nuclear factor of activated T cell c1 (NFATc1) and osteoclast-associated receptor (OSCAR), two indispensable molecules for osteoclast differentiation. Furthermore, Menéndez et al. [8] showed that, through up-regulating MafB expression, retinoid X receptors (RXR) inhibited osteoclast differentiation and mediated bone homeostasis in osteoporosis model mice. From the above study, it is clear that MafB function as a negative regulator of osteoclastogenesis.