ABSTRACT
A series of experimental methods including 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide, alkaline phosphatase (ALP) activity measurement, alizarin red S stain and measurement, quantitative real-time reverse transcriptase polymerase chain reaction, and Western blot analysis were employed to assess the effects of LaCl3 on the proliferation, osteogenic differentiation, and mineralization of a murine preosteoblast cell line MC3T3-E1 at cell and molecular levels. The results indicated that LaCl3 had dual effects on the proliferation, osteogenic differentiation, and mineralization of MC3T3-E1 cells. First, LaCl3 promoted the proliferation, osteogenic differentiation, and mineralization of MC3T3-E1 cells at lower concentrations, then had no effects and further turned to inhibit the proliferation, osteogenic differentiation, and mineralization of MC3T3-E1 cells with increasing concentrations. The expression of runt-related transcription factor 2 (Runx2), bone morphogenetic protein 2 (BMP2), ALP, bone sialoprotein (BSP), collagen I (Col I), and osteocalcin (OCN) genes was upregulated in the presence of 0.0001 and 0.1 µM LaCl3, but these genes were downregulated in the MC3T3-E1 cells treated with 1,000 µM LaCl3. In addition, the expression of BMP2, Runx2, and OCN proteins was promoted by LaCl3 at the concentration of 0.0001 µM, but these proteins were downregulated after 1,000 µM LaCl3 treatment. The results suggest that LaCl3 likely up- or downregulates the expression of Runx2, which subsequently up- or downregulates osteoblasts marker genes Col I and BMP2 at early stages and ALP and OCN at later stages of differentiation, thus causes to promote or inhibit the proliferation, osteogenic differentiation and mineralization of MC3T3-E1 cells. The results will be helpful for understanding the mechanisms of bone metabolism and application of lanthanum-based compounds in the future.
Subject(s)
Bone Resorption/chemically induced , Calcification, Physiologic/drug effects , Down-Regulation/drug effects , Lanthanum/pharmacology , Osteoblasts/drug effects , Osteogenesis/drug effects , Up-Regulation/drug effects , Animals , Biomarkers/metabolism , Bone Morphogenetic Protein 2/biosynthesis , Bone Morphogenetic Protein 2/genetics , Bone Morphogenetic Protein 2/metabolism , Bone Resorption/metabolism , Cell Line , Cell Proliferation/drug effects , Collagen Type I/biosynthesis , Collagen Type I/genetics , Collagen Type I/metabolism , Core Binding Factor Alpha 1 Subunit/biosynthesis , Core Binding Factor Alpha 1 Subunit/genetics , Core Binding Factor Alpha 1 Subunit/metabolism , Hormesis , Lanthanum/poisoning , Mice , Osmolar Concentration , Osteoblasts/cytology , Osteocalcin/biosynthesis , Osteocalcin/genetics , Osteocalcin/metabolism , Osteopontin/biosynthesis , Osteopontin/genetics , Osteopontin/metabolism , RNA, Messenger/metabolismABSTRACT
A 60-year-old male subject who worked as a movie projectionist and who was exposed for 12 years to rare earths (RE) containing dusts from cored arc light carbon electrodes was investigated. Chest X-ray films and pulmonary function tests showed an interstitial lung disease, emphysema and a severe obstructive impairment with marked decrease of carbon monoxide diffusion capacity. The histological examination of a transbronchial biopsy confirmed the diffuse interstitial lung fibrosis. Neutron activation analysis (NAA) of the biopsy showed concentrations of cerium (Ce), lanthanum (La), neodimium (Nd), samarium (Sm), terbium (Tb) and ytterbium (Yb) which were high compared to the corresponding elements in the transbronchial biopsies of 5 unexposed subjects as a control group. Thorium (Th) (which is generally present as an impurity of the RE compounds) was also determined in order to estimate the radiation dose in the lung of the worker. On the basis of the clinical observations, of the analytical results by neutron activation analysis of RE and of the presence of Th in the transbronchial biopsy, as well as of the differential diagnosis, which tended to exclude other occupational or non-occupational lung diseases, a relation between the observed interstitial lung fibrosis and occupational exposure to RE is highly probable.
Subject(s)
Cerium/poisoning , Lung Diseases, Interstitial/chemically induced , Metals, Rare Earth/poisoning , Occupational Diseases/chemically induced , Occupational Exposure/adverse effects , Biopsy , Humans , Lanthanum/poisoning , Lung/pathology , Lung Diseases, Interstitial/diagnosis , Male , Middle Aged , Neodymium/poisoning , Neutron Activation Analysis , Respiratory Function Tests , Samarium/poisoning , Terbium , Thorium , YtterbiumABSTRACT
Serum ornithine carbamoyltransferase (OCT) in rats poisoned with lanthanum, cerium and praseodymium. Acta Physiol. Pol., 1977, 28 (6): 589-594. The serum ornithine carbamoyltransferase in relation to doses of lanthanum, cerium and praseodymium, administered intravenously as chlorides, was investigated. A directly proportional relationship was found between the doses of these compounds and the serum enzyme level in rats. The lowest doses at which a rise in the serum OCT level occured were determined. They were: lanthanum - 0.75 mg/kg of body weight, cerium - 1.5 mg/kg, and praseodymium - 3 mh/kg. A decreasing toxicity of these elements with increasing value of atomic number was observed.
