scholarly journals Medication-Related Osteonecrosis of the Jaws Initiated by Zoledronic Acid and Potential Pathophysiology

2021 ◽  
Vol 9 (8) ◽  
pp. 85
Author(s):  
Aya Alsalih ◽  
Annica Dam ◽  
Pia Lindberg ◽  
Anna Truedsson
Keyword(s):  
Zoledronic Acid ◽  
Dental Pulp ◽  
Bone Remodelling ◽  
Osteonecrosis Of The Jaw ◽  
Inclusion Criteria ◽  
Cellular Mechanisms ◽  
Osteonecrosis Of The Jaws ◽  
Current Review ◽  
Dose Dependent

The aim of this systematic review is to present an up-to-date review of available publications investigating the cellular mechanisms initiating the development of medication-related osteonecrosis of the jaw caused by zoledronic acid. Electronic searches of MEDLINE/PubMed and Scopus were conducted on the 3 June, 2019. A total of 804 publications were identified, of which 11 met the inclusion criteria and were, therefore, included in this study. All the included studies were in vitro studies investigating various human cells. The current review found that zoledronic acid in various concentrations increased apoptosis and decreased migration and proliferation of epithelial cells, fibroblasts, osteoblasts, endothelial cells and dental pulp stem cells, which can affect local tissue homeostasis. The consequences of zoledronic acid were found to be both time- and dose-dependent. The pathophysiology of medication-related osteonecrosis of the jaw is likely a multifactorial process involving prolonged wound healing, chronic inflammation and altered bone remodelling following the administration of zoledronic acid. Further research is needed to identify the exact pathophysiology to optimise management and treatment.

Zoledronic Acid Inhibits Osteoclastogenesis in Vitro and in a Mouse Model of Inflammatory Osteolysis

2003 ◽  
Vol 112 (9) ◽  
pp. 780-786 ◽  
Author(s):  
Holger Sudhoff ◽  
Brian T. Faddis ◽  
Jae Y. Jung ◽  
Henning Hildmann ◽  
Jörg Ebmeyer ◽  
...  
Keyword(s):  
Zoledronic Acid ◽  
Bone Marrow Cells ◽  
Mineral Apposition Rate ◽  
Tunel Staining ◽  
Tartrate Resistant Acid Phosphatase ◽  
Mouse Bone Marrow ◽  
Dependent Manner ◽  
Dose Dependent

This study assessed effects of the bisphosphonate zoledronic acid (ZLNA) on osteoclastogenesis. To assess the effect of ZLNA on osteoclast formation in vitro, we cultured mouse bone marrow cells under conditions that promote osteoclastogenesis. Administered at concentrations from 10−6 to 10−9 mol/L, ZLNA led to a dose-dependent inhibition of osteoclastogenesis. Combined TUNEL staining and histochemical staining for tartrate-resistant acid phosphatase showed that ZLNA induced apoptosis in osteoclasts and monocytic precursor cells. To study the effects of ZLNA in vivo, we placed keratin particles onto the surface of the parietal bone of mice to induce localized inflammatory bone resorption. Three experimental groups received daily subcutaneous injections of ZLNA (1, 3, or 10 μg/kg body weight) from 4 days before surgery until 5 days after keratin implantation. The ZLNA significantly reduced osteoclast recruitment in a dose-dependent manner, but did not affect the degree of inflammation or the mineral apposition rate.

scholarly journals Influences of Compressive Force and Zoledronic Acid on Osteoblast Proliferation and Differentiation: An In Vitro Study

2021 ◽  
Vol 11 (23) ◽  
pp. 11273
Author(s):  
Kazuyuki Yusa ◽  
Shigeo Ishikawa ◽  
Tomoharu Hemmi ◽  
Hiroshi Takano ◽  
Masayuki Fukuda ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Zoledronic Acid ◽  
Osteoblast Differentiation ◽  
Compressive Force ◽  
In Vitro Study ◽  
Osteonecrosis Of The Jaw ◽  
Alizarin Red ◽  
Matrix Mineralization ◽  
Proliferation And Differentiation

This study investigates the effects of zoledronic acid (ZA) and compressive force on osteoblast functions, to elucidate the pathogenesis of medication-related osteonecrosis of the jaw (MRONJ). MC3T3-E1 cells were exposed to ZA (1, 10 and 100 µM) to evaluate the effects of ZA on cell proliferation. Furthermore, to investigate the influence of ZA with or without compressive force on osteoblast differentiation, real-time polymerase chain reaction and Alizarin Red S staining were performed. ZA concentrations > 10 μM were highly cytotoxic to MC3T3-E1 cells. Combining 1-μM ZA with compressive force influenced expression levels of osteoblast-related genes and matrix mineralization. The inhibitory effects of ZA on cell proliferation and the combination of ZA and compressive force on osteoblast differentiation may contribute to the pathogenesis of MRONJ.

Somatostatin inhibits secretin-induced ductal hypercholeresis and exocytosis by cholangiocytes

1995 ◽  
Vol 269 (1) ◽  
pp. G110-G118 ◽  
Author(s):  
P. S. Tietz ◽  
G. Alpini ◽  
L. D. Pham ◽  
N. F. Larusso
Keyword(s):  
Bile Flow ◽  
Receptor Gene ◽  
Somatostatin Receptor ◽  
Cellular Mechanisms ◽  
Maximal Increase ◽  
Rnase Protection ◽  
Duct Ligation ◽  
Dose Dependent

Previous work from our laboratory has implicated hormone-induced plasma membrane movement (i.e., endo- and exocytosis) in water and electrolyte transport by the epithelial cells that line the ducts in the liver (i.e., cholangiocytes). To further explore the cellular mechanisms regulating ductal bile secretion, we infused somatostatin and/or secretin intravenously into rats 2 wk after either bile duct ligation (BDL), a procedure that induces selective proliferation of cholangiocytes, or sham surgery and measured bile flow and biliary constituents. We also determined the effect of somatostatin on basal and secretin-induced exocytosis by purified cholangiocytes isolated from rat liver after BDL. Finally, we studied the expression of the somatostatin receptor gene by both ribonuclease (RNase) protection and nuclear run-on assays using cDNA encoding for two subtypes of the somatostatin receptor gene (i.e., SSTR1 and SSTR2). In vivo, somatostatin infusion caused a dose-dependent bicarbonate-poor decrease (57% maximal decrease below baseline; P < 0.05) in bile flow in BDL but not in sham-operated rats; in contrast, secretin caused a dose-dependent bicarbonate-rich choleresis (228% maximal increase above baseline; P < 0.05) in BDL but not in sham-operated rats. Simultaneous or prior infusion of somatostatin inhibited the secretin-induced hypercholeresis in BDL rats. In vitro, somatostatin had no effect on basal exocytosis by cholangiocytes isolated from BDL rats; however, somatostatin inhitibed (88% maximal inhibition; P < 0.05) secretin-induced exocytosis by cholangiocytes in a dose-dependent fashion. In addition, somatostatin inhibited secretin-induced increases in levels of adenosine 3',5'-cyclic monophosphate (cAMP) in cholangiocytes isolated from BDL rats.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Geranylgeraniol Restores Zoledronic Acid-Induced Efferocytosis Inhibition in Bisphosphonate-Related Osteonecrosis of the Jaw

2021 ◽  
Vol 9 ◽  
Author(s):  
Xin Chen ◽  
Weiwen Zhu ◽  
Rongyao Xu ◽  
Xin Shen ◽  
Yu Fu ◽  
...  
Keyword(s):  
Zoledronic Acid ◽  
Mouse Models ◽  
Osteonecrosis Of The Jaw ◽  
Severe Side Effect ◽  
Apoptotic Cells ◽  
Jnk Pathway ◽  
Term Administration ◽  
Underlying Mechanisms ◽  
Activation Conditions

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a severe side effect of long-term administration of bisphosphonates such as zoledronic acid (ZA), but its pathogenesis remains unclear. Impairment of the clearance of apoptotic cells (termed “efferocytosis”) by ZA may be associated with the pathogenesis of BRONJ. The aim of this study was to investigate whether ZA might inhibit macrophage efferocytosis and promote osteocytic apoptosis, and the underlying mechanisms responsible for the disturbing balance between clean and generation of osteocytic apoptosis. We found that ZA significantly promoted the apoptosis of osteocyte and pre-osteoblast via BRONJ mouse models and in vitro MC3T3-E1 but also inhibited the efferocytosis of macrophage on apoptotic cells. Moreover, supplement with geranylgeraniol (GGOH), a substrate analog for geranylgeranylation of Rac1, could restore Rac1 homeostasis and rescue macrophage efferocytosis. GGOH partially inhibits MC3T3-E1 apoptosis induced by ZA via downregulation of Rac1/JNK pathway. We also examined the Rac1 distribution and activation conditions in bone marrow-derived macrophages (BMDMs) and MC3T3-E1 under ZA treatment, and we found that ZA impaired Rac1 migration to BMDM membrane, leading to round appearance with less pseudopodia and efferocytosis inhibition. Moreover, ZA simultaneously activated Rac1, causing overexpression of P-JNK and cleaved caspase 3 in MC3T3-E1. Finally, the systemic administration of GGOH decreased the osteocytic apoptosis and improved the bone healing of the extraction sockets in BRONJ mouse models. Taken together, our findings provided a new insight and experimental basis for the application of GGOH in the treatment of BRONJ.

Ce1-хGdхOy Nanoparticles Stimulate Proliferation of Dental Pulp Stem Cells In Vitro

2017 ◽  
Vol 13 ◽  
pp. 26-31
Author(s):  
Anton L. Popov ◽  
Olga G. Tatarnikova ◽  
Nelly R. Popova ◽  
Irina I. Selezneva ◽  
Azamat Y. Akkizov ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cerium Oxide ◽  
Dental Pulp ◽  
Low Cost ◽  
Dependent Manner ◽  
Urgent Task ◽  
High Concentrations ◽  
Further Development ◽  
Dose Dependent

One of the main reasons for limiting the widespread clinical use of mesenchymal stem cells (MSCs) is a low speed of their proliferation in vitro. In this regard, the search for new safe and effective growth stimulants is an urgent task. In this study, we investigated the effect of nanocrystalline cerium oxide doped with gadolinium (Ce1-х Gdх Oy), on the morphofunctional characteristics and proliferative activity of MSCs derived from dental pulp. It was shown that the introduction of Ce1-х Gdх Oy nanoparticles into the culture of dental MSCs provides the activation of proliferation of the cells in a dose-dependent manner. High concentrations of Ce1-х Gdх Oy nanoparticles inhibit the proliferation of the cells; however, this does not lead to further development of apoptosis and cell death. The obtained results indicate that the nanocrystalline cerium oxide can be considered as a basis for the development of highly efficient and low-cost supplements for culturing MSCs.

scholarly journals Dose-dependent inhibitory effects of zoledronic acid on osteoblast viability and function in vitro

2015 ◽  
Vol 13 (1) ◽  
pp. 613-622 ◽  
Author(s):  
XIN HUANG ◽  
SHILONG HUANG ◽  
FENGJIN GUO ◽  
FEI XU ◽  
PENG CHENG ◽  
...  
Keyword(s):  
Zoledronic Acid ◽  
Inhibitory Effects ◽  
And Function ◽  
Dose Dependent

Increased Protein Synthesis by Human Platelets during Phagocytosis of Latex Particles in Vitro

1976 ◽  
Vol 35 (02) ◽  
pp. 350-357 ◽  
Author(s):  
Hana Bessler ◽  
Galila Agam ◽  
Meir Djaldetti
Keyword(s):  
Protein Synthesis ◽  
Fold Increase ◽  
Human Platelets ◽  
Polystyrene Latex ◽  
Latex Particles ◽  
The Third ◽  
Platelet Protein ◽  
Dose Dependent ◽  
Phagocytotic Activity

SummaryA three-fold increase of protein synthesis by human platelets during in vitro phagocytosis of polystyrene latex particles was detected. During the first two hours of incubation, the percentage of phagocytizing platelets and the number of latex particles per platelet increased; by the end of the third hour, the first parameter remained stable, while the number of latex particles per cell had decreased.Vincristine (20 μg/ml of cell suspension) inhibited platelet protein synthesis. This effect was both time- and dose-dependent. The drug also caused a decrease in the number of phagocytizing cells, as well as in their phagocytotic activity.

The Effect of Adrenaline Infusions on Blood Coagulation in Normal and Haemophilia B Dogs

1966 ◽  
Vol 15 (03/04) ◽  
pp. 349-364 ◽  
Author(s):  
A.H Özge ◽  
H.C Rowsell ◽  
H.G Downie ◽  
J.F Mustard
Keyword(s):  
Body Weight ◽  
Factor Viii ◽  
Factor Ix ◽  
Clotting Factor ◽  
Blood Ph ◽  
Order Of Magnitude ◽  
Dose Dependent ◽  
Generation Test ◽  
Plasma Activity

SummaryThe addition of trace amounts of adrenaline to whole blood in plasma in vitro increased factor VIII, factor IX and whole plasma activity in the thromboplastin generation test. This was dose dependent.Adrenaline infusions less than 22 (μg/kg body weight in normal dogs accelerated clotting, increased factor IX, factor VIII and whole plasma activity in the thromboplastin generation test and caused a fall in blood pH. In a factor IX deficient dog, there was no increase in factor IX activity. After adrenaline infusions, however, the other changes occurred and were of the same order of magnitude as in the normal. Adrenaline in doses greater than 22 μg/kg body weight did not produce as great an effect on clotting in normal or factor IX deficient dogs. The platelet count in the peripheral blood was increased following the infusion of all doses of adrenaline. These observations suggest that the accelerating effect of adrenaline on clotting is not mediated through increase in activity of a specific clotting factor.

Soluble Thrombomodulin Purified from Human Urine Exhibits a Potent Anticoagulant Effect In Vitro and In Vivo

1995 ◽  
Vol 73 (05) ◽  
pp. 805-811 ◽  
Author(s):  
Yasuo Takahashi ◽  
Yoshitaka Hosaka ◽  
Hiromi Niina ◽  
Katsuaki Nagasawa ◽  
Masaaki Naotsuka ◽  
...  
Keyword(s):  
Human Urine ◽  
Specific Activity ◽  
Anticoagulant Activity ◽  
Rabbit Lung ◽  
Soluble Thrombomodulin ◽  
Molecular Weights ◽  
Dose Dependent Fashion ◽  
Dose Dependent

SummaryWe examined the anticoagulant activity of two major molecules of soluble thrombomodulin purified from human urine. The apparent molecular weights of these urinary thrombomodulins (UTMs) were 72,000 and 79,000, respectively. Both UTMs showed more potent cofactor activity for protein C activation [specific activity >5,000 thrombomodulin units (TMU)/mg] than human placental thrombomodulin (2,180 TMU/mg) and rabbit lung thrombomodulin (1,980 TMU/mg). The UTMs prolonged thrombin-induced fibrinogen clotting time (>1 TMU/ml), APTT (>5 TMU/ml), TT (>5 TMU/ml) and PT (>40 TMU/ml) in a dose-dependent fashion. These effects appeared in the concentration range of soluble thrombomodulins present in human plasma and urine. In the rat DIC model induced by thromboplastin, administration of UTMs by infusion (300-3,000 TMU/kg) restored the hematological abnormalities derived from DIC in a dose-dependent fashion. These results demonstrate that UTMs exhibit potent anticoagulant and antithrombotic activities, and could play a physiologically important role in microcirculation.

Sign in / Sign up

Export Citation Format

Share Document