scholarly journals Osteoblast and Osteoclast Activity Affect Bone Remodeling Upon Regulation by Mechanical Loading-Induced Leukemia Inhibitory Factor Expression in Osteocytes

2020 ◽  
Vol 7 ◽  
Author(s):  
Jingke Du ◽  
Jiancheng Yang ◽  
Zihao He ◽  
Junqi Cui ◽  
Yiqi Yang ◽  
...  
Keyword(s):  
Bone Remodeling ◽  
Mechanical Loading ◽  
Leukemia Inhibitory Factor ◽  
Fluid Shear Stress ◽  
Bone Structure ◽  
Inhibitory Factor ◽  
Tartrate Resistant Acid Phosphatase ◽  
Osteoclast Activity ◽  
Microgravity Simulation

PurposeBone remodeling is affected by mechanical stimulation. Osteocytes are the primary mechanical load-sensing cells in the bone, and can regulate osteoblast and osteoclast activity, thus playing a key role in bone remodeling. Further, bone mass during exercise is also regulated by Leukemia inhibitory factor (LIF). This study aimed to investigate the role of LIF in the mechanical response of the bone, in vivo and in vitro, and to elucidate the mechanism by which osteocytes secrete LIF to regulate osteoblasts and osteoclasts.MethodsA tail-suspension (TS) mouse model was used in this study to mimic muscular disuse. ELISA and immunohistochemistry were performed to detect bone and serum LIF levels. Micro-computed tomography (CT) of the mouse femurs was performed to measure three-dimensional bone structure parameters. Fluid shear stress (FSS) and microgravity simulation experiments were performed to study mechanical stress-induced LIF secretion and its resultant effects. Bone marrow macrophages (BMMs) and bone mesenchymal stem cells (BMSCs) were cultured to induce in vitro osteoclastogenesis and osteogenesis, respectively.ResultsMicro-CT results showed that TS mice exhibited deteriorated bone microstructure and lower serum LIF expression. LIF secretion by osteocytes was promoted by FSS and was repressed in a microgravity environment. Further experiments showed that LIF could elevate the tartrate-resistant acid phosphatase activity in BMM-derived osteoclasts through the STAT3 signaling pathway. LIF also enhanced alkaline phosphatase staining and osteogenesis-related gene expression during the osteogenic differentiation of BMSCs.ConclusionMechanical loading affected LIF expression levels in osteocytes, thereby altering the balance between osteoclastogenesis and osteogenesis.

Responses of Bone Cells to Biomechanical Forces in Vitro

1999 ◽  
Vol 13 (1) ◽  
pp. 93-98 ◽  
Author(s):  
E.H. Burger ◽  
J. Klein-Nulend
Keyword(s):  
Nitric Oxide ◽  
Mechanical Loading ◽  
Cell Biology ◽  
Cellular Response ◽  
Fluid Shear Stress ◽  
Bone Structure ◽  
Bone Cells ◽  
Bone Adaptation

In this paper, we review recent studies of the mechanism by which mechanical loading of bone is transduced into cellular signals of bone adaptation. Current biomechanical theory and in vivo as well as in vitro experiments agree that the three-dimensional network of osteocytes and bone-lining cells provides the cellular basis for mechanosensing in bone, leading to adaptive bone (re)modeling. They also agree that flow of interstitial fluid through the lacunar-canalicular porosity of bone, as a result of mechanical loading, most likely provides the stimulus for mechanosensing, and informs the bone cellular network about the adequacy of the existing bone structure. Important signaling molecules involved in in vivo adaptive bone formation, as well as in in vitro cellular response to fluid flow, are nitric oxide and prostaglandins. The expression of key enzymes for nitric oxide and prostaglandin production in bone cells is altered by fluid shear stress in vitro. Together, these studies have increased our understanding of the cell biology underlying Wolff's Law. This may lead to new strategies for combating disuse-related osteoporosis, and may also be of use in understanding and predicting the long-term integration of bone-replacing implants.

Endometrial leukemia inhibitory factor as a predictor of pregnancy after in vitro fertilization

2008 ◽  
Vol 102 (1) ◽  
pp. 23-27 ◽  
Author(s):  
Paulo Serafini ◽  
André M. Rocha ◽  
Cyntia T. Osório ◽  
Ismael da Silva ◽  
Eduardo L. Motta ◽  
...  
Keyword(s):  
In Vitro Fertilization ◽  
Leukemia Inhibitory Factor ◽  
Inhibitory Factor ◽  
Vitro Fertilization

Stem cell factor and leukemia inhibitory factor promote primordial germ cell survival by suppressing programmed cell death (apoptosis)

Development ◽  
1993 ◽  
Vol 118 (4) ◽  
pp. 1089-1094 ◽  
Author(s):  
M. Pesce ◽  
M.G. Farrace ◽  
M. Piacentini ◽  
S. Dolci ◽  
M. De Felici
Keyword(s):  
Cell Death ◽  
Stem Cell ◽  
Programmed Cell Death ◽  
Leukemia Inhibitory Factor ◽  
Stem Cell Factor ◽  
Tissue Transglutaminase ◽  
Primordial Germ Cell ◽  
Inhibitory Factor ◽  
High Level

Proliferating primordial germ cells (PGCs) isolated from mouse embryos soon after their arrival in the genital ridges would only survive in vitro at temperature of less than 30 degrees C (De Felici, M. and McLaren, A. (1983). Exp. Cell. Res. 144, 417–427; Wabik-Sliz, B. and McLaren, A. (1984). Exp. Cell. Res. 154, 530–536) or when co-cultured on cell feeder layers (Donovan, P. J., Stott, D., Godin, I., Heasman, J. and Wylie, C. C. (1986). Cell 44, 831–838; De Felici, M. and Dolci, S. (1991). Dev. Biol. 147, 281–284). In the present paper we report that mouse PGC death in vitro occurs with all the hallmarks of programmed cell death or apoptosis. We found that after 4–5 hours in culture many PGCs isolated from 12.5 dpc fetal gonads assumed a nuclear morphology and produced membrane bound fragments (apoptotic bodies) typical of apoptotic cells. In addition, PGCs in culture accumulated high level of tissue transglutaminase (tTGase; an enzyme that is induced and activated during apoptosis) and showed extensive degradation of DNA to oligonucleosomal fragments, which is characteristic of apoptosis. The physiological relevance of this mechanism of PGC death is supported by the finding that some PGCs undergoing apoptosis, as revealed by the high level of tTGase expression, were detected in the embryo. Most importantly, we show that the addition of stem cell factor (SCF) or leukemia inhibitory factor (LIF) to the culture medium, two cytokines known to favour PGC survival and/or proliferation in vitro, markedly reduced the occurrence of apoptosis in PGCs during the first hours in culture.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Murine leukemia inhibitory factor enhances retroviral-vector infection efficiency of hematopoietic progenitors

Blood ◽  
1990 ◽  
Vol 76 (6) ◽  
pp. 1098-1103 ◽  
Author(s):  
FA Fletcher ◽  
DE Williams ◽  
C Maliszewski ◽  
D Anderson ◽  
M Rives ◽  
...  
Keyword(s):  
Leukemia Inhibitory Factor ◽  
Retroviral Vector ◽  
Inhibitory Factor ◽  
Hematopoietic Progenitors ◽  
Short Term ◽  
Infection Efficiency ◽  
Integration Sites ◽  
In Vitro Effects ◽  
Short Term Culture

Abstract We have investigated the in vitro effects of the cytokine leukemia inhibitory factor (LIF) on normal murine hematopoietic progenitors by measuring recovery and retroviral vector infection efficiency of 13-day posttransplant, spleen-colony-forming cell (CFU-S 13) in short-term culture. Up to a twofold increase in CFU-S13 recovery was observed, from 9.7 x 10(-5) cells in untreated controls to 17.8 to 19.5 x 10(-5) cells, depending on the concentration of LIF. Histologic analysis of spleen colonies from control and LIF-treated marrows demonstrated that there was no detectable alteration in the differentiative potential of CFU-S13. The efficiency of CFU-S13 infection was increased from 15% in untreated controls to 84% to 91% in LIF-treated marrows. Analysis of proviral integration sites in spleen colonies indicated that some CFU- S13 precursors were infected in the LIF-treated marrows.

15. Cytokines regulate the production of leukemia inhibitory factor in human bone-derived cells in vitro

Bone ◽  
1991 ◽  
Vol 12 (4) ◽  
pp. 294-294
Author(s):  
D.B. Evans ◽  
A.G. Smiths ◽  
M.M. Williams ◽  
P.J. Rathjen ◽  
J.K. Heath ◽  
...  
Keyword(s):  
Leukemia Inhibitory Factor ◽  
Human Bone ◽  
Inhibitory Factor

Recombinant human leukemia inhibitory factor enhances the development of preimplantation mouse embryo in vitro

1999 ◽  
Vol 71 (4) ◽  
pp. 722-725 ◽  
Author(s):  
Horng-Der Tsai ◽  
Chi-Chen Chang ◽  
Yao-Yuan Hsieh ◽  
Hui-Yu Lo ◽  
Li-Wei Hsu ◽  
...  
Keyword(s):  
Mouse Embryo ◽  
Leukemia Inhibitory Factor ◽  
Inhibitory Factor ◽  
Human Leukemia ◽  
Preimplantation Mouse Embryo ◽  
Preimplantation Mouse

scholarly journals Osteocytes remodel bone by TGF-β-induced YAP/TAZ signaling

2019 ◽  
Author(s):  
Christopher D. Kegelman ◽  
Jennifer C. Coulombe ◽  
Kelsey M. Jordan ◽  
Daniel J. Horan ◽  
Ling Qin ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Bone Remodeling ◽  
Molecular Mechanisms ◽  
Bone Matrix ◽  
Protease Gene ◽  
Matrix Remodeling ◽  
Osteoclast Activity ◽  
Control Bone

ABSTRACTOsteocytes are bone matrix-entombed cells that form an interconnected network of processes called the lacunar/canalicular system, which enables osteocytes to coordinate bone formation and resorption. Osteocytes indirectly regulate osteoblast and osteoclast activity on bone surfaces but also directly resorb and deposit their surrounding bone matrix through perilacunar/canalicular remodeling. However, the molecular mechanisms by which osteocytes control bone remodeling remain unclear. We previously reported that the transcriptional regulators Yes-associated protein (YAP) and Transcriptional co-activator with PDZ-motif (TAZ) promote bone acquisition in osteoblast-lineage cells. Here, we tested the hypothesis that YAP and TAZ regulate osteocyte-mediated bone remodeling by conditional ablation of both YAP and TAZ from mouse osteocytes using 8kb-DMP1-Cre. Osteocyte conditional YAP/TAZ deletion reduced bone mass and dysregulated matrix collagen content and organization, which together impaired bone mechanical properties. YAP/TAZ deletion reduced osteoblast number and activity and increased osteoclast activity. In addition, YAP/TAZ deletion directly impaired osteocyte lacunar/canalicular network remodeling, reducing canalicular density, length, and branching, but did not alter lacunar size or shape. Further, consistent with recent studies identifying TGF-β signaling as a key inducer of perilacunar/canalicular remodeling through expression of matrix-remodeling enzymes, YAP/TAZ deletion in vivo decreased osteocyte expression of matrix proteases Mmp13, Mmp14, and Cathepsin K. In vitro, pharmacologic inhibition of YAP/TAZ transcriptional activity in osteocyte-like cells abrogated TGF-β-induced protease gene expression. Together, these data show that YAP and TAZ act downstream of TGF-β in osteocytes to control bone matrix accrual, organization, and mechanical properties indirectly by coordinating osteoblast/osteoclast activity and directly by regulating perilacunar/canalicular remodeling.

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