scholarly journals The Role of BMP Signaling in Osteoclast Regulation

2021 ◽  
Vol 9 (3) ◽  
pp. 24
Author(s):  
Brian Heubel ◽  
Anja Nohe
Keyword(s):  
Bone Formation ◽  
Bone Morphogenetic Proteins ◽  
Bone Diseases ◽  
Bmp Signaling ◽  
Bone Homeostasis ◽  
Direct Stimulation ◽  
Federal Drug Administration ◽  
Bmp Pathway ◽  
Stimulation Of

The osteogenic effects of Bone Morphogenetic Proteins (BMPs) were delineated in 1965 when Urist et al. showed that BMPs could induce ectopic bone formation. In subsequent decades, the effects of BMPs on bone formation and maintenance were established. BMPs induce proliferation in osteoprogenitor cells and increase mineralization activity in osteoblasts. The role of BMPs in bone homeostasis and repair led to the approval of BMP2 by the Federal Drug Administration (FDA) for anterior lumbar interbody fusion (ALIF) to increase the bone formation in the treated area. However, the use of BMP2 for treatment of degenerative bone diseases such as osteoporosis is still uncertain as patients treated with BMP2 results in the stimulation of not only osteoblast mineralization, but also osteoclast absorption, leading to early bone graft subsidence. The increase in absorption activity is the result of direct stimulation of osteoclasts by BMP2 working synergistically with the RANK signaling pathway. The dual effect of BMPs on bone resorption and mineralization highlights the essential role of BMP-signaling in bone homeostasis, making it a putative therapeutic target for diseases like osteoporosis. Before the BMP pathway can be utilized in the treatment of osteoporosis a better understanding of how BMP-signaling regulates osteoclasts must be established.

The emerging role of Interleukin 37 in bone homeostasis and inflammatory bone diseases

2021 ◽  
Vol 98 ◽  
pp. 107803
Author(s):  
Peiyao Wu ◽  
Jieyu Zhou ◽  
Yafei Wu ◽  
Lei Zhao
Keyword(s):  
Bone Diseases ◽  
Bone Homeostasis

scholarly journals Inhibitory Effect of (2R)-4-(4-hydroxyphenyl)-2-butanol 2-O-β-d-apiofuranosyl-(1→6)-β-d-glucopyranoside on RANKL-Induced Osteoclast Differentiation and ROS Generation in Macrophages

2020 ◽  
Vol 22 (1) ◽  
pp. 222
Author(s):  
Eun-Nam Kim ◽  
Ga-Ram Kim ◽  
Jae Sik Yu ◽  
Ki Hyun Kim ◽  
Gil-Saeng Jeong
Keyword(s):  
Bone Loss ◽  
Bone Formation ◽  
Bone Disease ◽  
Osteoclast Differentiation ◽  
Inhibitory Effect ◽  
Bone Diseases ◽  
Ros Generation ◽  
Bone Homeostasis ◽  
Disease Treatment ◽  
And Migration

In bone homeostasis, bone loss due to excessive osteoclasts and inflammation or osteolysis in the bone formation process cause bone diseases such as osteoporosis. Suppressing the accompanying oxidative stress such as ROS in this process is an important treatment strategy for bone disease. Therefore, in this study, the effect of (2R)-4-(4-hydroxyphenyl)-2-butanol 2-O-β-d-apiofuranosyl-(1→6)-β-d-glucopyranoside (BAG), an arylbutanoid glycoside isolated from Betula platyphylla var. japonica was investigated in RANKL-induced RAW264.7 cells and LPS-stimulated MC3E3-T1 cells. BAG inhibited the activity of TRAP, an important marker of osteoclast differentiation and F-actin ring formation, which has osteospecific structure. In addition, the protein and gene levels were suppressed of integrin β3 and CCL4, which play an important role in the osteoclast-induced bone resorption and migration of osteoclasts, and inhibited the production of ROS and restored the expression of antioxidant enzymes such as SOD and CAT lost by RANKL. The inhibitory effect of BAG on osteoclast differentiation and ROS production appears to be due to the inhibition of MAPKs phosphorylation and NF-κβ translocation, which play a major role in osteoclast differentiation. In addition, BAG inhibited ROS generated by LPS and effectively restores the mineralization of lost osteoblasts, thereby showing the effect of bone formation in the inflammatory situation accompanying bone loss by excessive osteoclasts, suggesting its potential as a new natural product-derived bone disease treatment.

BMP and Ihh/PTHrP signaling interact to coordinate chondrocyte proliferation and differentiation

Development ◽  
2001 ◽  
Vol 128 (22) ◽  
pp. 4523-4534 ◽  
Author(s):  
Eleonora Minina ◽  
Hans Markus Wenzel ◽  
Conny Kreschel ◽  
Seth Karp ◽  
William Gaffield ◽  
...  
Keyword(s):  
Bone Morphogenetic Proteins ◽  
Feedback Loop ◽  
Bmp Signaling ◽  
Signaling Systems ◽  
Chondrocyte Maturation ◽  
Parathyroid Hormone Related Protein ◽  
Proliferation And Differentiation ◽  
Mouse Limb ◽  
Pthrp Expression

During endochondral ossification, two secreted signals, Indian hedgehog (Ihh) and parathyroid hormone-related protein (PTHrP), have been shown to form a negative feedback loop regulating the onset of hypertrophic differentiation of chondrocytes. Bone morphogenetic proteins (BMPs), another family of secreted factors regulating bone formation, have been implicated as potential interactors of the Ihh/PTHrP feedback loop. To analyze the relationship between the two signaling pathways, we used an organ culture system for limb explants of mouse and chick embryos. We manipulated chondrocyte differentiation by supplementing these cultures either with BMP2, PTHrP and Sonic hedgehog as activators or with Noggin and cyclopamine as inhibitors of the BMP and Ihh/PTHrP signaling systems. Overexpression of Ihh in the cartilage elements of transgenic mice results in an upregulation of PTHrP expression and a delayed onset of hypertrophic differentiation. Noggin treatment of limbs from these mice did not antagonize the effects of Ihh overexpression. Conversely, the promotion of chondrocyte maturation induced by cyclopamine, which blocks Ihh signaling, could not be rescued with BMP2. Thus BMP signaling does not act as a secondary signal of Ihh to induce PTHrP expression or to delay the onset of hypertrophic differentiation. Similar results were obtained using cultures of chick limbs. We further investigated the role of BMP signaling in regulating proliferation and hypertrophic differentiation of chondrocytes and identified three functions of BMP signaling in this process. First we found that maintaining a normal proliferation rate requires BMP and Ihh signaling acting in parallel. We further identified a role for BMP signaling in modulating the expression of Ihh. Finally, the application of Noggin to mouse limb explants resulted in advanced differentiation of terminally hypertrophic cells, implicating BMP signaling in delaying the process of hypertrophic differentiation itself. This role of BMP signaling is independent of the Ihh/PTHrP pathway.

Replicating the Role of the Human Retina for a Cortical Visual Neuroprosthesis

2013 ◽  
pp. 1532-1551
Author(s):  
Samuel Romero ◽  
Christian Morillas ◽  
Antonio Martínez ◽  
Begoña del Pino ◽  
Francisco Pelayo ◽  
...  
Keyword(s):  
Visual Cortex ◽  
Significant Degree ◽  
Research Field ◽  
Human Retina ◽  
Direct Stimulation ◽  
Biologically Inspired ◽  
Visual Inputs ◽  
Response Modeling ◽  
Stimulation Of

Neuroengineering is an emerging research field combining the latest findings from neuroscience with developments in a variety of engineering disciplines to create artificial devices, mainly for therapeutical purposes. In this chapter, an application of this field to the development of a visual neuroprosthesis for the blind is described. Electrical stimulation of the visual cortex in blind subjects elicits the perception of visual sensations called phosphenes, a finding that encourages the development of future electronic visual prostheses. However, direct stimulation of the visual cortex would miss a significant degree of image processing that is carried out by the retina. The authors describe a biologically-inspired retina-like processor designed to drive the implanted stimulator using visual inputs from one or two cameras. This includes dynamic response modeling with minimal latency. The outputs of the retina-like processor are comparable to those recorded in biological retinas that are exposed to the same stimuli and allow estimation of the original scene.

scholarly journals The Role of NLRP3 Inflammasome Activities in Bone Diseases and Vascular Calcification

Inflammation ◽  
2020 ◽  
Author(s):  
Chenyang Yu ◽  
Caihua Zhang ◽  
Zhihui Kuang ◽  
Qiang Zheng
Keyword(s):  
Vascular Calcification ◽  
Nlrp3 Inflammasome ◽  
Periodontal Diseases ◽  
Bone Destruction ◽  
Bone Diseases ◽  
Sterile Inflammation ◽  
Inflammatory Factors ◽  
Bone Homeostasis ◽  
Caspase 1

Abstract Continuous stimulation of inflammation is harmful to tissues of an organism. Inflammatory mediators not only have an effect on metabolic and inflammatory bone diseases but also have an adverse effect on certain genetic and periodontal diseases associated with bone destruction. Inflammatory factors promote vascular calcification in various diseases. Vascular calcification is a pathological process similar to bone development, and vascular diseases play an important role in the loss of bone homeostasis. The NLRP3 inflammasome is an essential component of the natural immune system. It can recognize pathogen-related molecular patterns or host-derived dangerous signaling molecules, recruit, and activate the pro-inflammatory protease caspase-1. Activated caspase-1 cleaves the precursors of IL-1β and IL-18 to produce corresponding mature cytokines or recognizes and cleaves GSDMD to mediate cell pyroptosis. In this review, we discuss the role of NLRP3 inflammasome in bone diseases and vascular calcification caused by sterile or non-sterile inflammation and explore potential treatments to prevent bone loss.

scholarly journals A Survey of Strategies to Modulate the Bone Morphogenetic Protein Signaling Pathway: Current and Future Perspectives

2016 ◽  
Vol 2016 ◽  
pp. 1-15 ◽  
Author(s):  
Jonathan W. Lowery ◽  
Brice Brookshire ◽  
Vicki Rosen
Keyword(s):  
Bone Morphogenetic Proteins ◽  
Bmp Signaling ◽  
Protein Signaling ◽  
Bone Morphogenetic Protein Signaling ◽  
Human Organ ◽  
Morphogenetic Protein ◽  
Organ Systems ◽  
Bmp Pathway ◽  
Wide Perspective ◽  
The Relationship

Bone morphogenetic proteins (BMPs) constitute the largest subdivision of the TGF-βfamily of ligands and are unequivocally involved in regulating stem cell behavior. Appropriate regulation of canonical BMP signaling is critical for the development and homeostasis of numerous human organ systems, as aberrations in the BMP pathway or its regulation are increasingly associated with diverse human pathologies. In this review, we provide a wide-perspective on strategies that increase or decrease BMP signaling. We briefly outline the current FDA-approved approaches, highlight emerging next-generation technologies, and postulate prospective avenues for future investigation. We also detail how activating other pathways may indirectly modulate BMP signaling, with a particular emphasis on the relationship between the BMP and Activin/TGF-βpathways.

Stimulation of steroid secretion by adrenocorticotropin injections and by arginine vasopressin infusions: no evidence for a direct stimulation of the human adrenal by arginine vasopressin

1991 ◽  
Vol 125 (4) ◽  
pp. 348-353 ◽  
Author(s):  
V. Bähr ◽  
J. Hensen ◽  
O. Hader ◽  
T. Bölke ◽  
W. Oelkers
Keyword(s):  
Arginine Vasopressin ◽  
Plasma Aldosterone ◽  
Regression Coefficients ◽  
Minor Importance ◽  
Cortisol Secretion ◽  
Plasma Acth ◽  
Direct Stimulation ◽  
Stimulatory Action ◽  
Stimulation Of

Abstract. Arginine vasopressin stimulates the secretion of adrenocorticotropin. A direct stimulatory effect of AVP on cortisol as well as aldosteron secretion has been postulated by several investigators. To study the possible role of a direct stimulatory action of AVP on the adrenal cortex, normal volunteers were treated with incremental injections of ACTH or with incremental infusions of AVP which raised plasma AVP levels to a maximum of 256±16 pmol/l. In both situations, a significant (p<0.001) linear correlation between plasma ACTH and plasma cortisol was observed. The regression coefficients were not different (p>0.5). Plasma aldosterone was stimulated by both treatments, but the weakly positive correlation between plasma ACTH and plasma aldosterone was not significant for either stimulus. Thus, in man, a direct stimulatory effect of AVP on cortisol secretion cannot be demonstrated. A direct effect of AVP on aldosterone cannot be definitely excluded, but is certainly of minor importance.

scholarly journals ARF6 stimulates clathrin/AP-2 recruitment to synaptic membranes by activating phosphatidylinositol phosphate kinase type Iγ

2003 ◽  
Vol 162 (1) ◽  
pp. 113-124 ◽  
Author(s):  
Michael Krauss ◽  
Masahiro Kinuta ◽  
Markus R. Wenk ◽  
Pietro De Camilli ◽  
Kohji Takei ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Synaptic Membranes ◽  
Direct Stimulation ◽  
Vesicle Membranes ◽  
Phosphatidylinositol Phosphate ◽  
Presynaptic Plasma Membrane ◽  
Phosphatidylinositol 4 ◽  
Adp Ribosylation Factor ◽  
Stimulation Of

Clathrin-mediated endocytosis of synaptic vesicle membranes involves the recruitment of clathrin and AP-2 adaptor complexes to the presynaptic plasma membrane. Phosphoinositides have been implicated in nucleating coat assembly by directly binding to several endocytotic proteins including AP-2 and AP180. Here, we show that the stimulatory effect of ATP and GTPγS on clathrin coat recruitment is mediated at least in part by increased levels of PIP2. We also provide evidence for a role of ADP-ribosylation factor 6 (ARF6) via direct stimulation of a synaptically enriched phosphatidylinositol 4-phosphate 5-kinase type Iγ (PIPKIγ), in this effect. These data suggest a model according to which activation of PIPKIγ by ARF6-GTP facilitates clathrin-coated pit assembly at the synapse.

scholarly journals The Role of BMP Signaling in Female Reproductive System Development and Function

2021 ◽  
Vol 22 (21) ◽  
pp. 11927
Author(s):  
Esmeralda Magro-Lopez ◽  
María Ángeles Muñoz-Fernández
Keyword(s):  
Bone Morphogenetic Proteins ◽  
Reproductive System ◽  
Transforming Growth Factor ◽  
Current Knowledge ◽  
System Development ◽  
Transforming Growth Factor Β ◽  
Bmp Signaling ◽  
Female Reproductive System ◽  
And Function

Bone morphogenetic proteins (BMPs) are a group of multifunctional growth factors that belong to the transforming growth factor-β (TGF-β) superfamily of proteins. Originally identified by their ability to induce bone formation, they are now known as essential signaling molecules that regulate the development and function of the female reproductive system (FRS). Several BMPs play key roles in aspects of reproductive system development. BMPs have also been described to be involved in the differentiation of human pluripotent stem cells (hPSCs) into reproductive system tissues or organoids. The role of BMPs in the reproductive system is still poorly understood and the use of FRS tissue or organoids generated from hPSCs would provide a powerful tool for the study of FRS development and the generation of new therapeutic perspectives for the treatment of FRS diseases. Therefore, the aim of this review is to summarize the current knowledge about BMP signaling in FRS development and function.

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