The Effects of Mn2+ on the Proliferation, Osteogenic Differentiation and Adipogenic Differentiation of Primary Mouse Bone Marrow Stromal Cells

The effects of Mn²⁺ on the proliferation, osteogenic and adipogenic differentiation of BMSCs were evaluated by employing MTT, ΔΨm, cell cycle, ALP activity, collagen production, ARS and oil red O stain assays. The results indicated that Mn²⁺ decreased the viability at most concentrations for 24 h, but the viability was increased with prolonging incubation time. Mn²⁺ at the concentrations of 1?×?10^-7 and 1?×?10^-6?mol/L decreased ΔΨm in the BMSCs for 48 h. Mn²⁺ induced G2/M phase cell cycle arrest at tested concentrations. On day 7 and 10, the effect of Mn²⁺ on the osteogenic differentiation depended on concentration, but it inhibited osteogenic differentiation at all tested concentrations for 14 d. The effect of Mn²⁺ on the synthesis of collagen of BMSCs depended on concentration for 7 d, but Mn²⁺ inhibited the synthesis of collagen at all tested concentrations for 10 d. On day 14, Mn²⁺ inhibited the formation of mineralized matrix nodules of BMSCs at all tested concentrations, the inhibitory effect turned to be weaker with prolonging incubation time. Mn²⁺ promoted the adipogenic differentiation of BMSCs at all tested concentrations for 10 d, but had no effect with prolonging incubation time. These findings suggested the effects of Mn²⁺ on the proliferation, osteogenic differentiation and adipogenic differentiation of BMSCs are very complicated, concentration and incubation time are key factors for switching the biological effects of Mn²⁺ from damage to protection.     

Expression, Purification, and Characterization of a Dentin Phosphoprotein Produced by Escherichia coli, and Its Odontoblastic Differentiation Effects on Human Dental Pulp Cells

To investigate the functions of recombinant human dentin phosphoprotein (rhDPP), we examined cell adhesion, viability and the odontoblastic differentiation activity of human dental pulp cells (hDPCs). Firstly, rhDPP was constructed using pBAD-HisA plasmid in Escherichia coli. Cell adhesion and viability of hDPCs by rhDPP was examined using a crystal violet assay and a MTT assay, ALP, mineralization activity and odontoblastic differentiation-related mRNA levels of hDPCs were measured to elucidate the odontoblastic differentiation effect of rhDPP on hDPCs. Initially, rhDPP significantly and dose-dependently increased hDPCs adhesion versus the untreated control (p?<?0.05). Cell viability was also significantly increased by rhDPP at 5?days (p?<?0.001). Furthermore, the odontoblastic differentiation effect of rhDPP was verified by measuring ALP activity, mineralization activity and the mRNA levels of odontoblastic differentiation markers. Taken together, rhDPP is expected to play an important role on hDPCs, thereby suggesting its potential use for tooth repair and regeneration.     

Three‐dimensional (3‐D) fluorescence spectroscopy analysis of the fluorescent dissolved organic matter released by the marine toxic dinoflagellate Alexandrium catenella exposed to metal stress by zinc or lead

We investigated the effects of zinc or lead on growth and on exudation of fluorescent dissolved organic matter (FDOM) by the marine toxic dinoflagellate Alexandrium catenella (Whedon & Kofoid) Balech. The species was exposed to increasing free zinc (1.34 × 10^?7 M–3.98 × 10^?6 M) or lead (5.13 × 10^?9 M–1.82 × 10^?7 M) concentra‐tions. Low metal levels ([Zn²⁺] = 1.34 × 10^?7 M; [Pb²⁺] = 5.13 × 10^?9 M) had no effect on cell growth. Toxic effects were observed from higher metal contamination ([Zn²⁺] = 3.98 × 10^?6 M; [Pb²⁺] = 6.54 × 10^?8 M), as a conversion of vegetative cells into cysts. Analysis of the released FDOM by three‐dimensional (3‐D) fluorescence spectroscopy was achieved, using the parallel factor analysis (PARAFAC). The PARAFAC modeling revealed four components associated with two contributions: one related to the biological activity; the other linked to the organic matter decomposition in the culture medium. The C1 component combined a tryptophan peak and characteristics of humic substances, whereas the C2 component was considered as a tryptophan protein fluorophore. The two others C3 and C4 components were associated with marine organic matter production. Relea‐sed fluorescent substances were induced by low ([Zn²⁺]= 1.34 × 10^?7 M; [Pb²⁺] = 5.13 × 10^?9 M) and moderate ([Zn²⁺] = 6.21 × 10^?7 M; [Pb²⁺] = 2.64× 10^?9 M) metal concentrations, suggesting the activation of cellular mechanisms in response to metal stress, to exudate FDOM that could complex metal cations and reduce their toxicity toward A. catenella cells.     

Effects of extracellular calcium on viability and osteogenic differentiation of bone marrow stromal cells in vitro

Bone marrow stromal cells (BMSCs) have been extensively used for tissue engineering. However, the effect of Ca²⁺ on the viability and osteogenic differentiation of BMSCs has yet to be evaluated. To determine the dose-dependent effect of Ca²⁺ on viability and osteogenesis of BMSCs in vitro, BMSCs were cultured in calcium-free DMEM medium supplemented with various concentrations of Ca²⁺ (0, 1, 2, 3, 4, and 5 mM) from calcium citrate. Cell viability was analyzed by MTT assay and osteogenic differentiation was evaluated by alkaline phosphatase (ALP) assay, Von Kossa staining, and real-time PCR. Ca²⁺ stimulated BMSCs viability in a dose-dependent manner. At slightly higher concentrations (4 and 5 mM) in the culture, Ca²⁺ significantly inhibited the activity of ALP on days 7 and 14 (P < 0.01 or P < 0.05), significantly suppressed collagen synthesis (P < 0.01 or P < 0.05), and significantly elevated calcium deposition (P < 0.01) and mRNA levels of osteocalcin (P < 0.01 or P < 0.05) and osteopontin (P < 0.01 or P < 0.05). Therefore, elevated concentrations of extracellular calcium may promote cell viability and late-stage osteogenic differentiation, but may suppress early-stage osteogenic differentiation in BMSCs.     

GAMETOPHYTIC GROWTH BY MACROCYSTIS PYRIFERA (PHAEOPHYTA) IN RESPONSE TO VARIOUS IRON AND ZINC CONCENTRATIONS1

Batch culturing experiments were conducted to examine effects on Macrocystis pyrifera (L.) C. A. Agardh gametophytic growth of various iron and zinc concentrations in the chemically defined, artificial seawater medium, Aquil. A least squares fit of experimental data represented the relative importance of these micronutrient effects. Optimal iron and zinc concentrations in Aquil were estimated at 340 nM (7 × 10^?11 nM as [Fe³⁺]) and 135 nM (6 × 10^?2 nM as [Zn²⁺]), respectively.     

Waste water treatment and metal (Pb<Superscript>2+</Superscript>, Zn<Superscript>2+</Superscript>) removal by microalgal based stabilization pond system

A case study was undertaken for the treatment of domestic wastewater generated at village of Sanghol, Distt. Fatehgarh Sahib, Punjab (India), using a schematic designed algal and duckweed based stabilization pond system, which is discussed here for winter months only (November to March) as there was no growth of duckweeds and only algae dominated the whole system. A proficient increase in pH and dissolved oxygen was observed after the treatment with reduction in chemical oxygen demand and biochemical oxygen demand by 93% and 79% respectively. Chlorella sp. was the dominating algal species in the stabilization pond water during entire period and was studied for its Zn²⁺ and Pb²⁺ metal removal efficiency. 60–70% removal of Zn²⁺ was observed from culture medium containing 5–20 mg L^?1 Zn²⁺, which declined to 42% at 50 mg L^?1. A constant decline in cell number from 538 × 10⁵ to 8 × 10⁵ cells ml^?1 was observed indicating zinc toxicity to Chlorella. Lead was maximally removed by 66.3% from culture medium containing 1 mg L^?1. The lead removal efficiency was 45 50 % at higher 5 to 20 mg L^?1 of external lead concentrations. The increase in cell number indicated no signs of Pb²⁺ toxicity up to 20 mg L^?1. The maximum uptake (q _max) by live Chlorella biomass for both Zn²⁺ and Pb²⁺ was 34.4 and 41.8 mg/g respectively.     

Zinc and salinity effects on membrane transport in Chara connivens

Pressure-probe measurements showed that the pressure relaxation of internodal cells of the freshwater alga Chara connivens slowed considerably when 1–5 mol m^?3 Zn²⁺, or more especially Zn²⁺ and 75 mol m^?3 NaCl, were present in the medium for periods of 1 h or longer. These results indicate that the water permeability of the Chara membrane is decreased by Zn²⁺, and that this effect is enhanced by 75 mol m^?3 NaCl. Specific values taken after 375 min exposure were: 5 mol m^?3 Zn²⁺ and 75 mol m^?3 NaCl caused the half-time for bulk water movement to increase from 7·8±2·3 to 79·5±5·4s, corresponding to a decrease in the hydraulic conductivity (Lp) from (13·0±3·3) × 10^?7 m s^?1 mPa^?1 to (1·25±0·23) × 10^?7 m s^?1 MPa^?1 (mean±S.D., n= 10). These changes are not seen in the presence of NaCl alone, and to a reduced extent in the presence of 5 mol m^?3Zn²⁺ alone (after 375 min, Lp was (2·4±0·1) × 10^?7 m s^?1 MPa^?1, mean±S.D., n = 6). Ca²⁺ cannot substitute for Zn²⁺, but seems to competitively inhibit Zn²⁺. There was another, kinetically distinct effect of Zn²⁺: the ingress of Na⁺ within 15 min of exposure to 75 mol m^?3 NaCl is halved by the presence of 1–5 mol m^?3 Zn²⁺, although internal osmolality is little changed by Zn²⁺. In spite of this, Zn²⁺ does not exert the long-term protection against NaCl that has been reported for Ca²⁺. Depending on the concentration of Zn²⁺ and the duration of the exposure, the effects on water permeability were fully or partly reversible within 24–48 h. The mechanism of these changes is difficult to identify. One possibility is a zinc-induced restriction of trans-membrane channels to give single-file channels which can be blocked by salt.     

Lipopolysaccharide upregulates the proliferation,migration, and odontoblastic differentiation of NG2+ cells from human dental pulp in vitro

NG2⁺ cells have been proven to differentiate into odontoblasts in vivo, and their contribution to odontoblasts is significantly increased, especially after tooth injury. However, their characteristics in vitro, especially under an inflammatory environment, are still not fully understood. Therefore, this study aimed to explore their proliferation, migration, and odontoblastic differentiation ability after treatment with lipopolysaccharide (LPS) in vitro. In our study, NG2 ⁺ cells were isolated from the human dental pulp by magnetic‐activated cell sorting, and these isolated cells were proven to be NG2 ⁺ by immunostaining. When compared with human dental pulp cells (hDPCs), the NG2 ⁺ cells showed no significant differences in cell migration with or without LPS incubation, but their proliferative ability was weaker. When treated with LPS, NG2 ⁺ cells expressed elevated levels of pro‐inflammatory cytokines including interleukin‐1β (IL‐1β), IL‐6, IL‐8, and tumor necrosis factor‐α, and among these, the expression of IL‐1β and IL‐6 were higher than that of hDPCs. Their multipotent differentiation potential was confirmed by the induction of odontoblastic and adipogenic differentiation, and LPS increased their odontoblastic differentiation capacity. In the odontoblastic differentiation process, Wnt5a, BMP2, and BMP7 mRNA were increased, while the canonical Wnt‐related genes were decreased. In conclusion, the LPS stimulation promotes the migration, proliferative, and odontoblastic differentiation ability of NG2 ⁺ cells from the human dental pulp in vitro, and bone morphogenetic protein and the noncanonical Wnt pathway may be involved in their odontoblastic differentiation. These results indicated their special roles in tooth injury repair and potential application in pulp regeneration.     

Magnesium Ions Promote the Biological Behaviour of Rat Calvarial Osteoblasts by Activating the PI3K/Akt Signalling Pathway

Magnesium has been investigated as a biodegradable metallic material. Increased concentrations of Mg²⁺ around magnesium implants due to biodegradation contribute to its satisfactory osteogenic capacity. However, the mechanisms underlying this process remain elusive. We propose that activation of the PI3K/Akt signalling pathway plays a role in the Mg²⁺-enhanced biological behaviours of osteoblasts. To test this hypothesis, 6, 10 and 18 mM Mg²⁺ was used to evaluate the stimulatory effect of Mg²⁺ on osteogenesis, which was assessed by evaluating cell adhesion, cell viability, ALP activity, extracellular matrix mineralisation and RT-PCR. The expression of p-Akt was also determined by western blotting. The results showed that 6 and 10 mM Mg²⁺ elicited the highest stimulatory effect on cell adhesion, cell viability and osteogenic differentiation as evidenced by cytoskeletal staining, MTT assay results, ALP activity, extracellular matrix mineralisation and expression of osteogenic differentiation-related genes. In contrast, 18 mM Mg²⁺ had an inhibitory effect on the behaviour of osteoblasts. Furthermore, 10 mM Mg²⁺ significantly increased the phosphorylation of Akt in osteoblasts. Notably, the aforementioned beneficial effects produced by 10 mM Mg²⁺ were abolished by blocking the PI3K/Akt signalling pathway through the addition of wortmannin. In conclusion, these results demonstrate that 6 mM and 10 mM Mg²⁺ can enhance the behaviour of osteoblasts, which is at least partially attributed to activation of the PI3K/Akt signalling pathway. Furthermore, a high concentration (18 mM Mg²⁺) showed an inhibitory effect on the biological behaviour of osteoblasts. These findings advance the understanding of cellular responses to biodegradable metallic materials and may attract greater clinical interest in magnesium.     

An Efficient Protocol for Ulmus minor Mill. Protoplast Isolation and Culture in Agarose Droplets

We describe here an efficient and reproducible protocol for isolation and culture of protoplasts from Ulmus minor. Different sources of donor tissues were tested for protoplast isolation: callus and juvenile leaves from in vitro and greenhouse plants. Several combinations and concentrations of hydrolytic enzymes were used. Comparative tests between Cellulase Onozuka R10 and Cellulase Onozuka RS were made and the last one proved to be more efficient. Both the pectinases used, Macerozyme Onozuka R10 and Pectinase (Sigma^®), were efficient in protoplast isolation and there was no need for a more active pectinase. In vitro leaves proved to be the best source for protoplast isolation and produced an average of 3.96 × 10⁷ protoplasts per gram of fresh weigh. Elm mesophyll protoplasts were cultured using the advantageous method of agarose droplets and a modification of the Kao and Michayluk culture medium, using two plating densities (1 × 10⁵ and 2 × 10⁵ protoplasts ml^?1). Protoplast division and evolution into colonies and microcalli was promoted in the agarose droplets plated at 2 × 10⁵ protoplasts ml^?1. Ten weeks after protoplast culture initiation a plating efficiency of 2.7% was attained and the bigger microcalli, with at least 0.5 mm diameter, were transferred to a solid medium previously used for the production of embryogenic callus.     

Enhancement of production and activity of alkaline zinc metalloprotease from <Emphasis Type="Italic">Salinivibrio proteolyticus</Emphasis> using low intensity direct electric current and zinc nanoparticles

Objectives

To improve the production and activity of an alkaline zinc metalloprotease from Salinivibrio proteolyticus in response to ZnSO₄ (ionic and nanoparticle forms) and low intensity direct electric current (LIDC).

Results

A DC of 50 µA for 10 min increased enzyme production from 35 to 53 U ml^?1 when applied to the stationary phase bacterial cells. Zn²⁺ improved enzyme production better than zinc nanoparticles (52 vs. 43.5 U ml^?1). Zinc nanoparticles (0.5 mM) added to an enzyme reaction mixture containing casein (0.65 %) and 20 mM Tris/HCl buffer (pH 8) improved enzyme activity more than Zn²⁺ (42 vs. 36 U ml^?1).

Conclusion

LIDC exposure (50 µA, 10 min) to the stationary phase bacterial cells increases metalloprotease production in Salinivibrio. A low concentration of zinc nanoparticles (0.5 mM) increases maximum enzyme activity.

     

Characterization of a vacuolar zinc transporter OZT1 in rice (Oryza sativa L.)

The CDF family is a ubiquitous family that has been identified in prokaryotes, eukaryotes, and archaea. Members of this family are important heavy metal transporters that transport metal ions out of the cytoplasm. In this research, a full length cDNA named Oryza sativa Zn Transporter 1 (OZT1) that closely related to rat ZnT-2 (Zn Transporter 2) gene was isolated from rice. The OZT1 encoding a CDF family protein shares 28.2 % ~ 84.3 % of identities and 49.3 % ~ 90.9 % of similarities with other zinc transporters such as RnZnT-2, HsZnT-8, RnZnT-8 and AtMTP1. OZT1 was constitutively expressed in various rice tissues. The OZT1 expression was significantly induced both in the seedlings of japonica rice Nipponbare and indica rice IR26 in response to Zn²⁺ and Cd²⁺ treatments. Besides, OZT1 expression was also increased when exposed to other excess metals, such as Cu²⁺, Fe²⁺ and Mg²⁺. Subcellular localization analysis indicated that OZT1 localized to vacuole. Heterologous expression of OZT1 in yeast increased tolerance to Zn²⁺ and Cd²⁺ stress but not the Mg²⁺ stress. Together, OZT1 is a CDF family vacuolar zinc transporter conferring tolerance to Zn²⁺ and Cd²⁺ stress, which is important to transporting and homeostasis of Zn, Cd or other heavy metals in plants.     

Co2+ binding to α-lactalbumin

α-Lactalbumin possesses multiple Zn²⁺ binding sites, with the strongest site having an affinity constant of 5×10⁵ M^?1 [Permyakovet al. (1991),J. Protein Chem. 100, 577]. The binding of zinc at secondary sites is accompanied by destabilization of the protein structure and progressive protein aggregation. This pronounced destabilization is reflected in a shift of the thermal denaturation transition temperature by more than 40°. The present work examines Co²⁺ binding to bovineα-lactalbumin, where for this analog of Zn²⁺, multiple binding sites were also found from spectrofluorimetric titrations. The strong site Co²⁺ binding constant was 1.3×10⁶ M^?1. However, in contrast to Zn²⁺ binding, Co²⁺ does not cause protein aggregation nor any significant thermal destabilization of the protein. Fluroescence energy transfer measurements between Tb³⁺ in the strong calcium site to Co²⁺ in the strong Zn²⁺ site gave a distance in the range of 14–18 Å, which was in excellent agreement with recent crystallographic data for humanα-lactalbumin [Renet al. (1993), J. Biol. Chem.268, 19292–19298] However, the X-ray structure did not identify the additional zinc sites found from earlier solution studies, presumably due to restrictive crystal packing interactions. The results from the current work confirm that the strong cobalt (zinc) site in solution is the same zinc site elucidated by X-ray crystallography.     

Role of Vanadium (V) in the Differentiation of C3H10t1/2 Cells Towards Osteoblast Lineage: A Comparative Analysis with Other Trace Elements

In recent time, vanadium compounds are being used as antidiabetic drug and in orthopedic implants. However, the exact role of this incorporated vanadium in improving the quality of bone structure and morphology is not known. The impact of vanadium ion was studied and compared to other trace metal ions with respect to the proliferation and osteoblast differentiation of C3H10t1/2 cells. Toxicity profile of these trace metal ions revealed a descending toxicity trend of Fe²⁺ > Zn²⁺ > Cu²⁺ > Co²⁺ > Mn²⁺ > V⁵⁺ > Cr²⁺. The effect of vanadium and other trace metal ions on osteoblast differentiation was evaluated by culturing the cells for 10 days in osteoblastic medium supplemented with different trace ions at concentrations lower than their cytotoxic doses. The results indicated that vanadium has maximum impact on the induction of osteoblast differentiation by upregulating alkaline phosphatase activity and mineralization by up to 145 and 150 %, respectively (p?<?0.05), over control. Cu²⁺ and Zn²⁺ had a mild inhibitory effect, while Mn²⁺, Fe²⁺, and Co²⁺ demonstrated a clear decrease in osteoblast differentiation when compared to the control. The data as presented here demonstrate that orthopedic implants, if supplemented with trace metals like vanadium, may provide a source of better model for bone formation and its turnover.     

Control of flagellar motility in Euglena and Chlamydomonas. Microinjection of EDTA, EGTA, Mn(2)+, and Zn(2)+.

When a Euglena, in a medium containing ATP, is microinjected with 7 × 10^?14 l of 0.02 M EDTA, which binds Ca²⁺ and Mg²⁺, flagellar motility stops. Flagellar arrest in Chlamydomonas occurs with the injection of 2 × 10^?14 l of 0.02 M EDTA. The injection of similar amounts (7 × 10^?14 l in Euglena and 3 × 10^?14 l in Chlamydomonas) of 0.02 M EGTA, which preferentially binds Ca²⁺, did not significantly alter flagellar motility. This suggests that a decrease in the internal Ca²⁺ concentration in Euglena or Chlamydomonas did not stimulate flagellar beating. Further, flagellar motility decreased when internal Mg²⁺ was chelated. The microinjection of Zn²⁺ into these cells caused a decrease in flagellar frequency analogous to the decrease in frequency caused by the injection of Ca²⁺ and EDTA. The microinjection of 7 × 10^?14 l of 0.2 M Mn²⁺ caused an approx. 1.5-fold increase in Euglena flagellar motility. Chlamydomonas flagella, which cease to beat upon impalement in an Mg²⁺-free medium, resume a flagellar frequency of 18 Hz when injected with 3 × 10^?14 l of 0.2 M Mn²⁺. In the experiments reported here, Mn²⁺ acts as an analog of Mg²⁺.     

Effects of some steroid hormones on head-to-head association in bovine spermatozoa

In the presence of 2 × 10^?6 M Ca²⁺ in Tris-buffered medium 0.5 × 10^?6 M, oestradiol-17β or corticosterone significantly increased the head-to-head association of washed bull spermatozoa; in the same concentration, testosterone and 5α-dihydrotestosterone had no significant effects, whereas progesterone significantly dissociated the associated spermatozoa. At 8 × 10^?6 M Ca²⁺ in the same medium, all five hormones increased the association to about the same level. In Tyrode solution with a Ca²⁺ concentration of 1.4 × 10^?3 M, oestradiol-17β and corticosterone acted as above, whereas progesterone and the two testosterones effected dissociation. In Tyrode solution each of the dissociating hormones was combined with oestradiol-17β. In each case a sum of the effects of the two hormones was obtained without any stimulation or inhibition. All five hormones still produced significant effects at 5 × 10^?7 M in Tyrode solution. A corresponding value for ATP was found at 1 × 10^?5 M.     

On the Purification and some Properties of 5′-Adenylic Acid-Deaminating Enzyme from Microsporum audouini

From culture broth of Microsporum audouini, 5′-adenylic acid-deaminating enzyme has been purified to about 600-fold. The pH optimum was found to be 5.0 in acetate, 5.5 in succinate, 5.7 in citrate buffer. Velocity constant was 1.83×10^?1 per minute. The optimal temperature was 40°C and activation energy was 15,000 calories. Michaelis-Menten constant was 6×10^?4 m. This enzyme preparation removes amino groups of 5′- AMP, ADP and ATP quickly, of adenosine, 3′-AMP, 5′-deoxyAMP and NAD slowly, but adenine, 2,6-diaminopurine, 2′-AMP and NADP were not deaminated. The enzyme activity was inhibited with F^?, pCMB, Fe^{+ + +}, Cu^{+ +} and Zn^{+ +}     

Effect of foliar spray of zinc on chloroplast β-carbonic anhydrase expression and enzyme activity in rice (Oryza sativa L.) leaves

The β-carbonic anhydrase (β-CA) is regarded as a zinc-containing enzyme involved in photosynthesis. Here, the rice plants of cv. N22 were treated with foliar spray at a Zn²⁺ concentration range from 0–35.0 mM during the tillering stage. The β-CA expression in the treated leaves was quantitatively determined by RT-qPCR and gel-based immunoblotting techniques, and its enzyme activity and relative chlorophyll concentration were measured. Results indicated that exogenous zinc could benefit rice plants at the tillering stage, particularly chloroplast β-CA with a fourfold enhancement in gene expression and a 14.6 % increase in its activity by treating the rice leaves with the 7.0-mM Zn²⁺ concentration, thereby promoting photosynthesis by a 19.4 % increase in relative chlorophyll concentration per unit leaf area. Results also showed that the application of Zn²⁺ at a concentration exceeding 7.0 mM could result in leaf senescence, and in some cases leaf hurts with significant inactivation (decreasing by approximately 70 %) of β-CA enzyme. It could be concluded that the application of 7.0-mM Zn²⁺ benefits rice plants at the tillering stage. The β-CA activity was associated with the catalytic microenvironment, thus providing an indicator for physiological response to exogenous zinc in rice.     

Thulium Ion Promotes Apoptosis of Primary Mouse Bone Marrow Stromal Cells

Bone is one of the main target organs for the lanthanides (Ln). Biodistribution studies of Tm-based compounds in vivo showed that bone had significant uptake. But the effect of Tm³⁺ on primary mouse bone marrow stromal cells (BMSCs) has not been reported. So we investigated the effect and underlying mechanisms of Tm³⁺ on BMSCs. Cell viability, cell apoptosis, reactive oxygen species (ROS) level, lactate dehydrogenase (LDH) activity and mitochondrial membrane potential (MMP) were studied. The results indicated that Tm³⁺ increased the viability of BMSCs at concentrations of 1?×?10^?7, 1?×?10^?6, 1?×?10^?5, and 1?×?10^?4 mol/L in a dose-dependent manner, turned to decrease the viability of BMSCs at the highest concentration of 1?×?10^?3 mol/L for 24, 48, and 72 h. Tm³⁺ at 1?×?10^?3 mol/L promoted apoptosis of BMSCs, increased the ROS and LDH levels, and decreased MMP in BMSCs. Taken together, we demonstrated that Tm³⁺ at 1?×?10^?3 mol/L might induce cellular apoptosis through mitochondrial pathway. These results may be helpful for more rational application of Tm-based compounds in the future.