scholarly journals The mammalian lectin galectin-8 induces RANKL expression, osteoclastogenesis, and bone mass reduction in mice

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Yaron Vinik ◽  
Hadas Shatz-Azoulay ◽  
Alessia Vivanti ◽  
Navit Hever ◽  
Yifat Levy ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Mass ◽  
Bone Marrow Cells ◽  
Direct Action ◽  
Primary Cultures ◽  
Mass Reduction ◽  
Rankl Expression ◽  
Receptor Complexes ◽  
Skeletal Integrity ◽  
Mammalian Lectin

Skeletal integrity is maintained by the co-ordinated activity of osteoblasts, the bone-forming cells, and osteoclasts, the bone-resorbing cells. In this study, we show that mice overexpressing galectin-8, a secreted mammalian lectin of the galectins family, exhibit accelerated osteoclasts activity and bone turnover, which culminates in reduced bone mass, similar to cases of postmenopausal osteoporosis and cancerous osteolysis. This phenotype can be attributed to a direct action of galectin-8 on primary cultures of osteoblasts that secrete the osteoclastogenic factor RANKL upon binding of galectin-8. This results in enhanced differentiation into osteoclasts of the bone marrow cells co-cultured with galectin-8-treated osteoblasts. Secretion of RANKL by galectin-8-treated osteoblasts can be attributed to binding of galectin-8 to receptor complexes that positively (uPAR and MRC2) and negatively (LRP1) regulate galectin-8 function. Our findings identify galectins as new players in osteoclastogenesis and bone remodeling, and highlight a potential regulation of bone mass by animal lectins.

scholarly journals Author response: The mammalian lectin galectin-8 induces RANKL expression, osteoclastogenesis, and bone mass reduction in mice

2015 ◽  
Author(s):  
Yaron Vinik ◽  
Hadas Shatz-Azoulay ◽  
Alessia Vivanti ◽  
Navit Hever ◽  
Yifat Levy ◽  
...  
Keyword(s):  
Bone Mass ◽  
Author Response ◽  
Mass Reduction ◽  
Rankl Expression ◽  
Mammalian Lectin

Resistance of bone marrow-derived macrophages to apoptosis is associated with the expression of X-linked inhibitor of apoptosis protein in primary cultures of bone marrow cells

2001 ◽  
Vol 353 (2) ◽  
pp. 299-306 ◽  
Author(s):  
Hong LIN ◽  
Catheryne CHEN ◽  
Ben D.-M. CHEN
Keyword(s):  
Bone Marrow ◽  
Caspase 3 ◽  
Bone Marrow Cells ◽  
Primary Cultures ◽  
Precursor Cells ◽  
Inhibitor Of Apoptosis ◽  
Caspase 9 ◽  
Prolonged Incubation ◽  
Inhibitor Of Apoptosis Protein ◽  
Apoptosis Protein

In this study we investigated the underlying mechanisms that confer resistance on mature macrophages with the use of macrophage colony-stimulating factor (M-CSF)-induced bone marrow-derived macrophages (BMDM). In the presence of M-CSF, immature precursor cells were induced to undergo proliferation and differentiation into mature macrophages in vitro with cell morphology similar to that of tissue macrophages by day 7Ő10. Immunoblot analyses showed that bone marrow precursors express appreciable levels of caspase-3 and caspase-9 but no or very low levels of c-fms (M-CSF receptor) and the apoptosis regulators X-linked inhibitor of apoptosis protein (XIAP), c-IAP-1, Bcl-2 and Bax. The differentiation of BMDM is associated with a steady and gradual increase in the levels of c-fms, XIAP, c-IAP-1, Bcl-2 and Bax, reaching maximal levels by day 7. However, the levels of caspase-3 and caspase-9 stayed essentially unchanged even after prolonged incubation (more than 10 days) with M-CSF. Unlike bone marrow precursor cells, mature BMDM (day 7Ő10) were resistant to apoptosis induced by M-CSF depletion, which includes the activation of caspase-3 and caspase-9 and the degradation of XIAP, Bcl-2 and Bax proteins in the process. Treatment of day 7 BMDM with XIAP anti-sense oligonucleotides (oligos), but not sense oligos, partly abolished their resistance to apoptosis. By using a gel-shift assay and a specific nuclear factor κB (NF-κB) inhibitor, we demonstrated that NF-κB activity is responsible for the up-regulation of XIAP in M-CSF-treated macrophages. In addition, treatment of starved macrophages with M-CSF induced a rapid phosphorylation of Akt kinase before the activation of NF-κB. Our results showed that XIAP is one of the anti-apoptotic regulators that confer resistance on mature macrophages by M-CSF.

scholarly journals ПОРІВНЯЛЬНА ХАРАКТЕРИСТИКА ФЕНОТИПОВИХ ЗМІН КУЛЬТУР КЛІТИН ЖИРОВОЇ ТКАНИНИ ТА КІСТКОВОГО МОЗКУ В ПРОЦЕСІ КУЛЬТИВУВАННЯ

2017 ◽  
pp. 113-119 ◽  
Author(s):  
В. В. Ковпак ◽  
О. С. Ковпак
Keyword(s):  
Bone Marrow ◽  
Adipose Tissue ◽  
Cell Cultures ◽  
Bone Marrow Cells ◽  
Primary Cultures ◽  
Tissue Cell ◽  
Adipose Tissue Cell ◽  
Polygonal Shape ◽  
Adipose Tissue Cells ◽  
Number Of Cells

У статті описані дані щодо зміни фенотипу культур клітин жирової тканини (ККЖТ) та кісткового мозку (КККМ) у процесі культивування. Дослідження первинних культур клітин кісткового мозку та жирової тканини щура показали, що вони морфологічно гетерогенні, у їх склад входили: невелика кількість клітин полігональної форми, а основну масу складали фібробластоподібні. За подальшого культивування відмічали процес переходу від гетерогенних культур на нульовому  пасажі до найбільш гомогенних у кінці дослідження. Нами були відмічені відмінності у імунофенотипі культур клітин кісткового мозку та жирової тканини, які не зникали з пасажами. This article describes the changes in phenotype of cultures of adipose tissue cells (ATCC) and bone marrow cells (BMCC) in the process of cultivation. Study of primary cultures of cells of the bone marrow and adipose tissue of rat has shown that they are morphologically heterogeneous, they included: a small number of cells of polygonal shape, and the bulk was fìbroblast-like cells. Process of transition from the heterogeneous cultures at zero passaging to the most homogeneous at the end of the study was noted during further cultivation. We noted differences in immunophenotype of bone marrow and adipose tissue cell cultures that did not disappear with passaging.

scholarly journals The nucleocytoplasmic shuttling protein CIZ reduces adult bone mass by inhibiting bone morphogenetic protein–induced bone formation

2005 ◽  
Vol 201 (6) ◽  
pp. 961-970 ◽  
Author(s):  
Mikihiko Morinobu ◽  
Tetsuya Nakamoto ◽  
Kazunori Hino ◽  
Kunikazu Tsuji ◽  
Zhong-Jian Shen ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Formation ◽  
Bone Mass ◽  
Mrna Expression ◽  
Bone Marrow Cells ◽  
Nucleocytoplasmic Shuttling ◽  
Morphogenetic Protein ◽  
Adult Bone ◽  
Deficient Mice

Osteoporosis is a major health problem; however, the mechanisms regulating adult bone mass are poorly understood. Cas-interacting zinc finger protein (CIZ) is a nucleocytoplasmic shuttling protein that localizes at cell adhesion plaques that form where osteoblasts attach to substrate. To investigate the potential role of CIZ in regulating adult bone mass, we examined the bones in CIZ-deficient mice. Bone volume was increased and the rates of bone formation were increased in CIZ-deficient mice, whereas bone resorption was not altered. CIZ deficiency enhanced the levels of mRNA expression of genes encoding proteins related to osteoblastic phenotypes, such as alkaline phosphatase (ALP) as well as osterix mRNA expression in whole long bones. Bone marrow cells obtained from the femora of CIZ-deficient mice revealed higher ALP activity in culture and formed more mineralized nodules than wild-type cells. CIZ deficiency enhanced bone morphogenetic protein (BMP)–induced osteoblastic differentiation in bone marrow cells in cultures, indicating that BMP is the target of CIZ action. CIZ deficiency increased newly formed bone mass after femoral bone marrow ablation in vivo. Finally, BMP-2–induced bone formation on adult mouse calvariae in vivo was enhanced by CIZ deficiency. These results establish that CIZ suppresses the levels of adult bone mass through inhibition of BMP-induced activation of osteoblasts.

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