scholarly journals Effects and Interaction of Icariin, Curculigoside, and Berberine in Er-Xian Decoction, a Traditional Chinese Medicinal Formula, on Osteoclastic Bone Resorption

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Liming Xue ◽  
Lei Jiao ◽  
Yin Wang ◽  
Yan Nie ◽  
Ting Han ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Resorption ◽  
Bone Marrow Cells ◽  
Cathepsin K ◽  
Osteoclastic Bone Resorption ◽  
Tartrate Resistant Acid Phosphatase ◽  
Inhibitory Effects ◽  
Dihydroxyvitamin D ◽  
Marrow Cells

Er-Xian decoction (EXD), a traditional Chinese medicine, has been reported to have a protective effect against bone loss in ovariectomized osteoporotic rats, and the inclusion of icariin (I), curculigoside (C), and berberine (B) in EXD displays inhibitory effects on osteoclastic bone resorption. In the present paper, we investigated the interaction and effects of I, C, B, and their combination on bone resorption activityin vitroon osteoclasts derived from rat bone marrow cells. ICB synergistically decreased the formation of bone resorption pits, the number of multinucleated osteoclasts, and the activity of tartrate-resistant acid phosphatase (TRAP) and showed antagonistic or additive effects on cathepsin K activity in the coculture system of osteoblasts and bone marrow cells in the presence of 1, 25-dihydroxyvitamin D3and dexamethasone. The combination of ICB also enhanced the inhibitory effects on the formation of F-actin ring, a cytoskeleton structure of osteoclasts induced from bone marrow cells with macrophage colony stimulation factor (M-CSF) and receptor activator of NF-κB ligand (RANKL). In addition, ICB synergistically improved the ratio of protein expression of osteoprotegerin (OPG) and RANKL in osteoblasts and interfered with the mitogen-activated protein kinases (MAPKs) pathway in osteoclast. These results clearly show that I, C, B, and their combination in EXD exert effects of mutual reinforcement. However, IBC does not show an intensified adverse effect in the ovariectomized murine model, as revealed by change in body and uterine weight, confirming the safety of EXD. These observations are in agreement with the rationality of the formula used in this paper.

Effects of Cyclic Pressure on Bone Marrow Cell Cultures

2002 ◽  
Vol 124 (3) ◽  
pp. 308-314 ◽  
Author(s):  
Jiro Nagatomi ◽  
Bernard P. Arulanandam ◽  
Dennis W. Metzger ◽  
Alain Meunier ◽  
Rena Bizios
Keyword(s):  
Bone Marrow ◽  
Bone Resorption ◽  
Mechanical Loading ◽  
Bone Marrow Cell ◽  
Cell Cultures ◽  
Bone Marrow Cells ◽  
Marrow Cell ◽  
Osteoclastic Bone Resorption ◽  
Cyclic Pressure ◽  
Marrow Cells

The present in-vitro study used bone marrow cell cultures and investigated the effects of cyclic pressure on osteoclastic bone resorption. Compared to control (cells maintained under static conditions), the number of tartrate resistant acid phosphatase (TRAP)-positive, osteoclastic cells was significantly p<0.05 lower when, immediately upon harvesting, bone marrow cells were exposed to cyclic pressure (10–40 kPa at 1.0 Hz). In contrast, once precursors in bone marrow cells differentiated into osteoclastic cells under static culture conditions for 7 days, subsequent exposure to the cyclic pressure of interest to the present study did not affect the number of osteoclastic cells. Most important, exposure of bone marrow cells to cyclic pressure for 1 h daily for 7 consecutive days resulted in significantly p<0.05 lower osteoclastic bone resorption and in lowered mRNA expression for interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-α), cytokines that are known activators of osteoclast function. In addition to unique contributions to osteoclast physiology, the present study provided new evidence of a correlation between mechanical loading and bone homeostasis as well as insight into the molecular mechanisms of bone adaptation to mechanical loading, namely cytokine-mediated control of osteoclast functions.

scholarly journals Crif1 Promotes Osteoporosis in Mice after Radiation

2019 ◽  
Author(s):  
Lixin Xiang ◽  
Li Chen ◽  
Yang Xiang ◽  
Fengjie Li ◽  
Xiaomei Zhang ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Resorption ◽  
Bone Loss ◽  
Bone Marrow Cells ◽  
Current Knowledge ◽  
Osteoclast Differentiation ◽  
Protein Docking ◽  
Rankl Expression ◽  
Marrow Cells

AbstractRadiation induces rapid bone loss and enhances bone resorption and RANKL expression. RANKL provides the crucial signal to induce osteoclast differentiation and plays an important role in bone resorption. However, the mechanisms of radiation-induced osteoporosis are not fully understood. Here, we show that Crif1 expression increases in bone marrow cells after radiation. Conditional Crif1 deletion in bone marrow cells causes decreases in RANKL expression and the RANKL/OPG ratio, and relieves bone loss after radiation in mice. We further demonstrated in vitro that Crif1 promotes RANKL secretion via the cAMP/PKA pathway. Moreover, protein-protein docking screening identified five compounds as Crif1 inhibitors; these compounds dramatically suppressed RANKL secretion and CREB phosphorylation when cells were exposed to forskolin. This study enriches current knowledge of the pathogenesis of osteoporosis and provides insights into potential therapeutic strategies for osteoporosis treatment.

scholarly journals Potentiation of antileukemic therapies by the dual PI3K/PDK-1 inhibitor, BAG956: effects on BCR-ABL– and mutant FLT3-expressing cells

Blood ◽  
2008 ◽  
Vol 111 (7) ◽  
pp. 3723-3734 ◽  
Author(s):  
Ellen Weisberg ◽  
Lolita Banerji ◽  
Renee D. Wright ◽  
Rosemary Barrett ◽  
Arghya Ray ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Tyrosine Kinase ◽  
Cell Lines ◽  
Myeloid Leukemia ◽  
Bone Marrow Cells ◽  
Akt Signaling ◽  
Inhibitory Effects ◽  
Marrow Cells

AbstractMediators of PI3K/AKT signaling have been implicated in chronic myeloid leukemia (CML) and acute myeloid leukemia (AML). Studies have shown that inhibitors of PI3K/AKT signaling, such as wortmannin and LY294002, are able to inhibit CML and AML cell proliferation and synergize with targeted tyrosine kinase inhi-bitors. We investigated the ability of BAG956, a dual PI3K/PDK-1 inhibitor, to be used in combination with inhibitors of BCR-ABL and mutant FLT3, as well as with the mTOR inhibitor, rapamycin, and the rapamycin derivative, RAD001. BAG956 was shown to block AKT phosphorylation induced by BCR-ABL–, and induce apoptosis of BCR-ABL–expressing cell lines and patient bone marrow cells at concentrations that also inhibit PI3K signaling. Enhancement of the inhibitory effects of the tyrosine kinase inhibitors, imatinib and nilotinib, by BAG956 was demonstrated against BCR-ABL expressing cells both in vitro and in vivo. We have also shown that BAG956 is effective against mutant FLT3-expressing cell lines and AML patient bone marrow cells. Enhancement of the inhibitory effects of the tyrosine kinase inhibitor, PKC412, by BAG956 was demonstrated against mutant FLT3-expressing cells. Finally, BAG956 and rapamycin/RAD001 were shown to combine in a nonantagonistic fashion against BCR-ABL– and mutant FLT3-expressing cells both in vitro and in vivo.

scholarly journals The Prenyl Group Contributes to Activities of Phytoestrogen 8-Prenynaringenin in Enhancing Bone Formation and Inhibiting Bone Resorption In Vitro

Endocrinology ◽  
2013 ◽  
Vol 154 (3) ◽  
pp. 1202-1214 ◽  
Author(s):  
Lei-Guo Ming ◽  
Xiang Lv ◽  
Xiao-Ni Ma ◽  
Bao-Feng Ge ◽  
Ping Zhen ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Mrna Expression ◽  
Bone Marrow Cells ◽  
Osteoclast Differentiation ◽  
Cathepsin K ◽  
Active Role ◽  
Osteoclast Formation ◽  
Calcium Deposition ◽  
Tartrate Resistant Acid Phosphatase

Abstract Previous studies have found that 8-prenylflavonoids have a higher osteogenic activity than do flavonoids, which suggested that the 8-prenyl group may play an active role in bone-protective properties. To address this hypothesis, activities of 8-prenylnaringenin (PNG) and naringenin (NG) in osteoblast and osteoclast differentiation and function were compared in vitro. PNG was found to have a stronger ability than NG to improve osteoblast differentiation and osteogenic function in cultured rat calvarial osteoblasts, as demonstrated by levels of alkaline phosphatase activity, osteocalcin, calcium deposition, and the number and area of mineralized bone nodules, as well as mRNA expression of osteogenesis-related genes Bmp-2, OSX, and Runx-2. In addition, although expression of osteoclastogenic inducer receptor activator of nuclear factor kappa-B ligand (RANKL) was not affected, that of osteoclastogenesis inhibitor osteoprotegerin (OPG) and consequently the OPG/RANKL ratio were increased, more potently by PNG than NG. PNG was also found to have a higher potency than NG in inhibiting the osteoclast formation in rabbit bone marrow cells and their resorptive activity, as revealed by lower numbers of osteoclasts formed, lower numbers and areas of bone resorption pits, and lower mRNA expression levels of tartrate-resistant acid phosphatase and cathepsin K. Furthermore, PNG induced apoptosis of mature osteoclasts at a higher degree and at an earlier time than did NG. These results indicate that the 8-prenyl group plays an important role and contributes to the higher bone-protective activity of PNG in comparison with NG.

scholarly journals Runx1-Mediated Regulation of Osteoclast Differentiation and Function

2014 ◽  
Vol 28 (4) ◽  
pp. 546-553 ◽  
Author(s):  
Do Y. Soung ◽  
Judith Kalinowski ◽  
Sanjeev K. Baniwal ◽  
Christian E. Jacome-Galarza ◽  
Baruch Frenkel ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Resorption ◽  
Bone Mass ◽  
Bone Marrow Cells ◽  
Osteoclast Formation ◽  
Mrna Levels ◽  
Metabolic Bone Diseases ◽  
And Function ◽  
Marrow Cells

Abstract Excessive bone resorption is the cause of several metabolic bone diseases including osteoporosis. Thus, identifying factors that can inhibit osteoclast formation and/or activity may define new drug targets that can be used to develop novel therapies for these conditions. Emerging evidence demonstrates that the master regulator of hematopoiesis, Runx1, is expressed in preosteoclasts and may influence skeletal health. To examine the potential role of Runx1 in osteoclast formation and function, we deleted its expression in myeloid osteoclast precursors by crossing Runx1 floxed mice (Runx1F/F) with CD11b-Cre transgenic mice. Mice lacking Runx1 in preosteoclasts (CD11b-Cre;Runx1F/F) exhibited significant loss of femoral trabecular and cortical bone mass compared with that in Cre-negative mice. In addition, serum levels of collagen type 1 cross-linked C-telopeptide, a biomarker of osteoclast-mediated bone resorption, were significantly elevated in CD11b-Cre;Runx1F/F mice compared with those in Runx1F/F mice. Tartrate-resistant acid phosphatase–positive osteoclasts that differentiated from bone marrow cells of CD11b-Cre;Runx1F/F mice in vitro were larger, were found in greater numbers, and had increased bone resorbing activity than similarly cultured cells from Runx1F/F mice. CD11b-Cre;Runx1F/F bone marrow cells that were differentiated into osteoclasts in vitro also had elevated mRNA levels of osteoclast-related genes including vacuolar ATPase D2, cathepsin K, matrix metalloproteinase 9, calcitonin receptor, osteoclast-associated receptor, nuclear factor of activated T cells cytoplasmic 1, and cFos. These data indicate that Runx1 expression in preosteoclasts negatively regulates osteoclast formation and activity and contributes to overall bone mass.

scholarly journals Interleukin-3 is significantly more effective than other colony- stimulating factors in long-term maintenance of human bone marrow- derived colony-forming cells in vitro

Blood ◽  
1989 ◽  
Vol 73 (7) ◽  
pp. 1836-1841 ◽  
Author(s):  
M Kobayashi ◽  
BH Van Leeuwen ◽  
S Elsbury ◽  
ME Martinson ◽  
IG Young ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cultured Cells ◽  
Bone Marrow Cells ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Interleukin 3 ◽  
Gm Csf ◽  
Factor G ◽  
Marrow Cells

Abstract Human bone marrow cells cultured for 21 days in the presence of recombinant human interleukin-3 (IL-3) produced up to 28 times more colony-forming cells (CFC) than could be obtained from cultures stimulated with granulocyte colony stimulating factor (G-CSF) or granulocyte-macrophage CSF (GM-CSF). IL-3-cultured cells retained a multipotent response to IL-3 in colony assays but were restricted to formation of granulocyte colonies in G-CSF and granulocyte or macrophage colonies in GM-CSF. Culture of bone marrow cells in IL-3 also led to accumulation of large numbers of eosinophils and basophils. These data contrast with the effects of G-CSF, GM-CSF, and IL-3 in seven-day cultures. Here both GM-CSF and IL-3 amplified total CFC that had similar multipotential colony-forming capability in either factor. G-CSF, on the other hand, depleted IL-3-responsive colony-forming cells dramatically, apparently by causing these cells to mature into granulocytes. The data suggest that a large proportion of IL-3- responsive cells in human bone marrow express receptors for G-CSF and can respond to this factor, the majority becoming neutrophils. Furthermore, the CFC maintained for 21 days in IL-3 may be a functionally distinct population from that produced after seven days culture of bone marrow cells in either IL-3 or GM-CSF.

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