scholarly journals Mechanical loading and how it affects bone cells: The role of the osteocyte cytoskeleton in maintaining our skeleton

2012 ◽  
Vol 24 ◽  
pp. 278-291 ◽  
Author(s):  
J Klein-Nulend ◽  
◽  
RG Bacabac ◽  
AD Bakker
Keyword(s):  
Mechanical Loading ◽  
Bone Cells

scholarly journals The Role of Connexin Channels in the Response of Mechanical Loading and Unloading of Bone

2020 ◽  
Vol 21 (3) ◽  
pp. 1146 ◽  
Author(s):  
Manuel A. Riquelme ◽  
Eduardo R. Cardenas ◽  
Huiyun Xu ◽  
Jean X. Jiang
Keyword(s):  
Mechanical Loading ◽  
Cell Function ◽  
Bone Cells ◽  
Bone Cell ◽  
Research Progress ◽  
Related Factor ◽  
Channel Network ◽  
Gap Junction Channel ◽  
Major Player

The skeleton adapts to mechanical loading to promote bone formation and remodeling. While most bone cells are involved in mechanosensing, it is well accepted that osteocytes are the principal mechanosensory cells. The osteocyte cell body and processes are surrounded by a fluid-filled space, forming an extensive lacuno-canalicular network. The flow of interstitial fluid is a major stress-related factor that transmits mechanical stimulation to bone cells. The long dendritic processes of osteocytes form a gap junction channel network connecting not only neighboring osteocytes, but also cells on the bone surface, such as osteoblasts and osteoclasts. Mechanosensitive osteocytes also form hemichannels that mediate the communication between the cytoplasmic and extracellular microenvironment. This paper will discuss recent research progress regarding connexin (Cx)-forming gap junctions and hemichannels in osteocytes, osteoblasts, and other bone cells, including those richly expressing Cx43. We will then cover the recent progress regarding the regulation of these channels by mechanical loading and the role of integrins and signals in mediating Cx43 channels, and bone cell function and viability. Finally, we will summarize the recent studies regarding bone responses to mechanical unloading in Cx43 transgenic mouse models. The osteocyte has been perceived as the center of bone remodeling, and connexin channels enriched in osteocytes are a likely major player in meditating the function of bone. Based on numerous studies, connexin channels may present as a potential new therapeutic target in the treatment of bone loss and osteoporosis. This review will primarily focus on Cx43, with some discussion in other connexins expressed in bone cells.

scholarly journals FRI0376 EFFECT OF CARBAMYLATED LOW-DENSITY LIPOPROTEINS ON BONE CELLS HOMEOSTASIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 784.2-785
Author(s):  
B. Lucchino ◽  
M. Leopizzi ◽  
T. Colasanti ◽  
V. DI Maio ◽  
C. Alessandri ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Bone Cells ◽  
Osteoclast Differentiation ◽  
Low Density Lipoproteins ◽  
Tartrate Resistant Acid Phosphatase ◽  
Low Density ◽  
Bone Homeostasis ◽  
Research Support ◽  
Erosive Disease

Background:Carbamylation is a post-translational modification occurring under several conditions such as uremia, smoking and chronic inflammation as in rheumatoid arthritis (RA). Low-density lipoproteins (LDL) represent a target of carbamylation. Carbamylated-LDL (cLDL) have an increased inflammatory and atherogenic potential. Growing evidence supports an influence of modified lipids on bone cells homeostasis. However, the role of cLDL on bone cells physiology is still unknown.Objectives:Considering the rate of carbamylation and the role of anti-carbamylated proteins antibodies as markers of erosive disease in RA, the purpose of this study is to investigate the effect of cLDL on bone homeostasis.Methods:In-vitrocarbamylation of LDL was performed as previously described by Ok et al. (Kidney Int. 2005). Briefly, native LDL (nLDL) were treated with potassium cyanate (KOCN) for 4 hours, followed by excessive dialysis for 36 hours to remove KOCN. Both osteoclasts (OCs) and osteoblasts (OBLs) were treated at baseline with 20 μg/ml, 100 μg/ml and 200 μg/ml of cLDL or nLDL. To induce osteoclast differentiation, CD14+ monocytes were isolated from peripheral blood of healthy donors by magnetic microbeads separation and then cultured on a 96-wells plate in DMEM media supplemented with RANKL and M-CSF. After 10 days cells were fixed, stained for tartrate-resistant acid phosphatase (TRAP), a marker of OC differentiation, and counted. OBLs were isolated from bone specimens of 3 patients who had undergone to knee or hip arthroplasty for osteoarthritis and treated for 5 days with different concentrations of cLDL and nLDL. OBLs were fixed and stained for alkaline phosphatase positive activity (ALP), a marker of osteogenic differentiation. Total RNA was extracted from cell lysates. Copies of single-stranded complementary DNA (cDNA) were synthesized and analyzed by real-time PCR to evaluate RANKL and Osteoprotegerin (OPG) mRNA expression levels.Results:In OCLs culture, cLDL significantly decreased the number of OC compared to untreated cells (200 μg/ml p=0,0015) and nLDL treated cells (200 μg/ml p= 0,011; 20 μg/ml p= 0,0014) (Fig 1). Moreover, treatment with cLDL induced an increase of not terminally differentiated OCs, reduced dimensions of OCs, less intense TRAP staining and vacuolization (Fig 2). In OBLs culture, cLDL (20, 100 μg/ml) significantly reduced the ALP activity of OBLs compared with untreated cells (p<0.05) (Fig 3). nLDL did not affect the ALP expression. Treatment with cLDL stimulated RANKL mRNA expression in osteoblasts increasing the RANKL/OPG ratio (Fig 4).Fig 1.Fig 2.Fig 3.Fig 4.Conclusion:cLDL induce a significant depression of OC and OBL differentiation. Moreover, cLDL increase RANKL expression in OBL, unbalancing bone tissue turnover towards bone resorption. Accordingly, cLDL could be implicated in the bone loss characterizing several conditions associated to an increased carbamylation, such as RADisclosure of Interests:Bruno Lucchino: None declared, Martina Leopizzi: None declared, Tania Colasanti: None declared, Valeria Di Maio: None declared, cristiano alessandri Grant/research support from: Pfizer, Guido Valesini: None declared, fabrizio conti Speakers bureau: BMS, Lilly, Abbvie, Pfizer, Sanofi, Manuela Di Franco: None declared, Francesca Romana Spinelli Grant/research support from: Pfizer, Consultant of: Novartis, Gilead, Lilly, Sanofi, Celgene, Speakers bureau: Lilly

Aging and the Osteogenic Response to Mechanical Loading

2001 ◽  
Vol 11 (s1) ◽  
pp. S137-S142 ◽  
Author(s):  
Wendy M. Kohrt
Keyword(s):  
Growth Factors ◽  
Bone Mass ◽  
Mechanical Loading ◽  
Bone Cells ◽  
Weight Bearing ◽  
Bone Modeling ◽  
Mineral Density ◽  
Increase Bone Mass ◽  
Age Related ◽  
Osteogenic Response

The osteogenic response to mechanical stress is blunted with aging. It has been postulated that this decline in responsiveness is related to (a) a limited ability to engender the strain necessary to reach the bone modeling threshold, due to decreased muscle mass and strength, and/or (b) a decline in certain hormones or growth factors that may interact with mechanical signals to change the sensitivity of bone cells to strain. There is reason to believe that both of these factors contribute to the reduced ability to increase bone mass through exercise with advancing age. Weight-bearing endurance exercise and resistance exercise have both been found to increase bone mass in older women and men. However, exercise training studies involving older individuals have generally resulted in increased bone mineral density only when the exercise is quite vigorous. There is also evidence that the osteogenic response to mechanical loading is enhanced by estrogens. Whether age-related changes in other factors (e.g., other hormones, growth factors, cytokines) also contribute to the reduced responsiveness of the aged skeleton to mechanical loading remains to be investigated.

Cultured bone cells from osteoporotic patients show an altered response to mechanical loading

1996 ◽  
Vol 6 (S1) ◽  
pp. 85-85
Author(s):  
J G H Sterck ◽  
J Klein-Nulend ◽  
P Lips ◽  
E H Burger
Keyword(s):  
Mechanical Loading ◽  
Bone Cells ◽  
Altered Response ◽  
Cultured Bone Cells

Calcium uptake by cultured bone cells: The role of phosphate, calcitonin and 1,25-(OH)2 D3

1975 ◽  
Vol 21 (1) ◽  
pp. 332-338 ◽  
Author(s):  
A. Harell ◽  
I. Binderman ◽  
M. Guez
Keyword(s):  
Calcium Uptake ◽  
Bone Cells ◽  
Cultured Bone Cells

The role of nervous system in adaptive response of bone to mechanical loading

2018 ◽  
Vol 234 (6) ◽  
pp. 7771-7780 ◽  
Author(s):  
Yini Qiao ◽  
Yang Wang ◽  
Yimei Zhou ◽  
Fulin Jiang ◽  
Tu Huang ◽  
...  
Keyword(s):  
Nervous System ◽  
Mechanical Loading ◽  
Adaptive Response

scholarly journals Lipids: Role in Embryonic Development (Review)

2019 ◽  
pp. 1-9
Author(s):  
Marisol León ◽  
A. C. B. Rodrigues ◽  
A. O. M. Turquetti ◽  
A. D. Cereta ◽  
L. F. Melo ◽  
...  
Keyword(s):  
Embryonic Development ◽  
Bone Cells ◽  
Bone Mineralization ◽  
Membrane Integrity ◽  
Cell Membrane Integrity ◽  
Muscle Formation ◽  
Neural Apoptosis ◽  
Neural Survival ◽  
Transport Molecules

Aims: We propose to briefly review the specific role of lipids in embryonic structures development. Results: Lipids are organic substances insoluble in water, divided into several classes, such as fatty acids, glycolipids, phospholipids, ceramides, sphingolipids, and stereo-lipids. They participate in processes of cellular metabolism and embryonic development which are associated with signalling, proliferation and cell migration. They act in developmental processes such as calcification and bone mineralization, pulmonary maturity, cellular differentiation, and neural survival, epithelial cells polarization and muscle formation, in which phospholipids as a major group, work more regularly. Lipids during embryonic development work directly as transport molecules or cell markers. In addition to an imbalance in its enzymatic and protein precursors (such as choline kinase), lipids can increase or decrease lipid concentration in cells, prevent its biotransformation, or affect its synergy with other molecules, leading to failures in the formation of organs such as the heart, brain, and bones. This aims to further the understanding of these processes and highlight its feasibility for future clinical applications. Conclusion: Lipids maintain cell membrane integrity in blastocysts, transport calcium to nerve and bone cells, facilitate neural apoptosis, and promote pulmonary maturation. These results aid in the understanding and prediction of alterations in lipidic metabolic syndromes in several pathological disorders during organ development.

scholarly journals HOW DO BONE CELLS SENSE MECHANICAL LOADING?

2009 ◽  
Vol 44 (4) ◽  
pp. 299-305 ◽  
Author(s):  
Carlos Vinícius Buarque de Gusmão ◽  
William Dias Belangero
Keyword(s):  
Mechanical Loading ◽  
Bone Cells

scholarly journals Implication of the p53-Related miR-34c, -125b, and -203 in the Osteoblastic Differentiation and the Malignant Transformation of Bone Sarcomas

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 810
Author(s):  
Camille Jacques ◽  
Robel Tesfaye ◽  
Melanie Lavaud ◽  
Steven Georges ◽  
Marc Baud’huin ◽  
...  
Keyword(s):  
Bone Cells ◽  
Osteoblastic Differentiation ◽  
Bone Diseases ◽  
Tumor Suppressor Protein ◽  
Genomic Integrity ◽  
Potential Implication ◽  
Cycle Arrest ◽  
Transcriptional Regulatory ◽  
Bone Sarcomas

The formation of the skeleton occurs throughout the lives of vertebrates and is achieved through the balanced activities of two kinds of specialized bone cells: the bone-forming osteoblasts and the bone-resorbing osteoclasts. Impairment in the remodeling processes dramatically hampers the proper healing of fractures and can also result in malignant bone diseases such as osteosarcoma. MicroRNAs (miRNAs) are a class of small non-coding single-strand RNAs implicated in the control of various cellular activities such as proliferation, differentiation, and apoptosis. Their post-transcriptional regulatory role confers on them inhibitory functions toward specific target mRNAs. As miRNAs are involved in the differentiation program of precursor cells, it is now well established that this class of molecules also influences bone formation by affecting osteoblastic differentiation and the fate of osteoblasts. In response to various cell signals, the tumor-suppressor protein p53 activates a huge range of genes, whose miRNAs promote genomic-integrity maintenance, cell-cycle arrest, cell senescence, and apoptosis. Here, we review the role of three p53-related miRNAs, miR-34c, -125b, and -203, in the bone-remodeling context and, in particular, in osteoblastic differentiation. The second aim of this study is to deal with the potential implication of these miRNAs in osteosarcoma development and progression.

The Role of Mechanical Loading in Ligament Tissue Engineering

2009 ◽  
Vol 15 (4) ◽  
pp. 467-475 ◽  
Author(s):  
Hugh A. Benhardt ◽  
Elizabeth M. Cosgriff-Hernandez
Keyword(s):  
Tissue Engineering ◽  
Mechanical Loading ◽  
Ligament Tissue Engineering
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