Biomedical subjects

V Katavić

Publications and source records attributed to V Katavić.

7 recordsLinked to original sources

PubMed2006

Activated T lymphocytes suppress osteoclastogenesis by diverting early monocyte/macrophage progenitor lineage commitment towards dendritic cell differentiation through down-regulation of receptor activator of nuclear factor-kappaB and c-Fos.

Activated T lymphocytes either stimulate or inhibit osteoclastogenesis from haematopoietic progenitors in different experimental models. To address this controversy, we used several modes of T lymphocyte activation in osteoclast differentiation--mitogen-pulse, anti-CD3/CD28 stimulation and in vivo and in vitro alloactivation. Osteoclast-like cells were generated from non-adherent immature haematopoietic monocyte/macrophage progenitors in murine bone-marrow in the presence of receptor activator of nuclear factor (NF)-kappaB ligand (RANKL) and monocyte-macrophage colony-stimulating factor (M-CSF). All modes of in vivo and in vitro T lymphocyte activation and both CD4(+) and CD8(+) subpopulations produced similar inhibitory effects on osteoclastogenesis paralleled by enhanced dendritic cell (DC) differentiation. Osteoclast-inhibitory effect was associated with T lymphocyte activation and not proliferation, and could be replaced by their culture supernatants. The stage of osteoclast differentiation was crucial for the inhibitory action of activated T lymphocytes on osteoclastogenesis, because the suppressive effect was visible only on early osteoclast progenitors but not on committed osteoclasts. Inhibition was associated specifically with increased granulocyte-macrophage colony-stimulating factor (GM-CSF) expression by the mechanism of progenitor commitment toward lineages other than osteoclast because activated T lymphocytes down-regulated RANK, CD115, c-Fos and calcitonin receptor expression, and increased differentiation towards CD11c-positive DC. An activated T lymphocyte inhibitory role in osteoclastogenesis, confirmed in vitro and in vivo, mediated through GM-CSF release, may be used to counteract activated bone resorption mediated by T lymphocyte-derived cytokines in inflammatory and immune disorders. We also demonstrated the importance of alloactivation in osteoclast differentiation and the ability of cyclosporin A to abrogate T lymphocyte inhibition of osteoclastogenesis, thereby confirming the functional link between alloreaction and bone metabolism.

Animals↗

PubMed2005

Alteration of newly induced endochondral bone formation in adult mice without tumour necrosis factor receptor 1.

Tumour necrosis factor (TNF)-alpha, a major proinflammatory cytokine, exerts its role on bone cells through two receptors (TNFR1 and TNFR2). TNFR1, but not TNFR2, is expressed by osteoblasts and its function in bone formation in vivo is not fully understood. We compared in vivo new bone formation in TNFR1-deficient (TNFR1(-/-)) mice and wild-type mice, using two models of bone formation: intramembranous ossification following tibial marrow ablation and endochondral ossification induced by bone morphogenetic protein (BMP)-2. Intramembranous osteogenesis in TNFR1(-/-) mice did not differ from the wild-type mice either in histomorphometric parameters or mRNA expression of bone-related markers and inflammatory cytokines. During endochondral osteogenesis, TNFR1(-/-) mice formed more cartilage (at post-implantation day 9), followed by more bone and bone marrow (at day 12). mRNAs for BMP-2, -4 and -7 were increased during the endochondral differentiation sequence in TNFR1(-/-) mice. The expression of receptor activator of NF-kappa B ligand (RANKL) and receptor activator of NF-kappa B (RANK), as assessed by quantitative reverse transcription polymerase chain reaction (RT-PCR), was also increased significantly during endochondral ossification in TNFR1(-/-) mice. In conclusion, signalling through the TNFR1 seems to be a negative regulator of new tissue formation during endochondral but not intramembranous osteogenesis in an adult organism. BMPs and RANKL and its receptor RANK may be involved in the change of local environment in the absence of TNFR1 signalling.

Animals↗

PubMed2001

Weekly quizzes in extended-matching format as a means of monitoring students' progress in gross anatomy.

We compared weekly quizzes in extended-matching format with multiple-choice questions and oral examinations as means of monitoring students' progress in gross anatomy. Students' performance on 19 weekly oral examinations or 10-question quizzes based on extended-matching or multiple-choice formats were correlated with their success on 3 interim examinations and the final comprehensive examination. The Kuder-Richardson formula 20, an estimate of precision of the test, was 0.64 for extended-matching quizzes. Students' performance on interim examinations did not differ significantly. There was a significant correlation between students' mean scores on weekly quizzes and mean scores on interim examinations in both the extended-matching (r = 0.516) and multiple-choice group (r = 0.823). The mean grades (ranging from 2 to 5) on the final exam, based on understanding of anatomical concepts and their application in clinical practice, were significantly higher in extended-matching group (4.8) than in the multiple-choice (4.1) and orally examined groups (3.9) (p < 0.05). We conclude that extended-matching quizzes were at least as effective as multiple-choice quizzes and oral examinations and may be better for acquiring synthetic understanding of anatomical concepts especially in combination with other means of knowledge assessment. We recommend them as a reliable and objective means of monitoring students' performance during a gross anatomy course.

Anatomy↗

PubMed2001

Cellular and molecular interactions between immune system and bone.

Functional interdependence between immune and bone systems is reflected in a number of regulatory molecules acting on the cells of both systems and common precursors for bone and immune cells. Therefore, the disturbances of the immune system may affect bone metabolism, and vice versa. This review addresses the roles of two major immune cell populations, T and B lymphocytes, in the regulation of bone metabolism. Experimental models and human diseases demonstrated that T lymphocytes may produce many bone cell regulatory cytokines, including two essential stimulators of osteoclastogenesis: receptor for activation of nuclear factor kappa b (NF-kappa B) (RANK) ligand (RANKL) and macrophage colony-stimulating factor. The effect of T lymphocytes on osteoclastogenesis may be both stimulatory and inhibitory, and depends on the activation stage and pattern of cytokine production. We showed that acute removal of T lymphocytes stimulated osteoclast differentiation in vitro and enhanced new cartilage and bone formation at non-osseous sites in vivo. B lymphocytes may be even more closely related to bone cells, as B lymphopoiesis requires an intimate contact with osteoblastic/stromal cells, and estrogens, powerful regulators of bone mass, are also involved in the differentiation of the B lymphocyte lineage. Also, B lymphocyte progenitors may give rise to functional osteoclasts. Both B and T lymphocytes may act through the RANKL/RANK/osteoprotegerin cytokine system, which has been independently discovered within immune and bone systems. These cytokines have crucial roles in the development and function of osteoclasts, dendritic cells, and T and B lymphocytes, as well as in the thymus and lymph node organogenesis. The cytokines produced by immune cells may affect bone cell function and vice versa, but the full complexity of these interactions awaits further investigation.

Animals↗

PubMed1999

Genetic variability of new bone induction in mice.

We studied differences in ectopic osteoinduction in eight mouse inbred strains and an outbred strain. Antigen-extracted autolyzed rat bone gelatin was implanted under hind limb muscle fascia of 12-week-old males, and new bone formation was morphologically assessed on serial sections. Four weeks after implantation, less than half of the implants from CBA/J, A/J, BALB/cJ, and C3Hf/Bu mice showed induction of only cartilage. New cartilage was observed in all, and bone and bone marrow in 80% of the implants from AKR/J, C57BL/6J, DBA/2J, and RFM/Rij mice. Volume of the newly formed tissue ranged from 1.3% of the old matrix in A/J strain to 74.6% in DBA/2J strain. Outbred CD1 mice showed only weak cartilage induction. The "good" responders differed among themselves in the volume and type of newly induced tissue: DBA/2J, RFM/Rij, and AKR/J mice had a similar ratio of new bone and cartilage and abundant bone marrow, whereas the predominant newly induced tissue in C57Bl/6J mice was cartilage. The pattern of the expression of BMP-2, -4, and -7, alkaline phosphatase, osteocalcin, interferon-gamma, and granulocyte-macrophage colony-stimulating factor, measured by reverse transcriptase polymerase chain reaction, did not correlate with the type and the quantity of the newly induced tissue. Our results show that adult mice of inbred strains differ not only in the peak bone mass and morphology, but also ability to form new bone after an osteoinductive stimulus. Ectopic osteoinduction may be a useful in vivo model to investigate genetic determinants of endochondral osteogenesis, especially its immunological component.

Animals↗

PubMed1995

Bone turnover in homozygous beta 2-microglobulin knock-out mice does not differ from that of their heterozygous littermates.

beta 2-Microglobulin is a constituent of the class I major histocompatibility complex (MHC) molecule and crucial for its normal function in cell recognition. It has also been isolated from bone and shown to regulate bone metabolism and to be altered in various bone diseases. In order to further investigate the role of the immune system in bone metabolism, we studied basic properties of bone physiology in beta 2-microglobulin-deficient mice created by the technique of gene knock-out. Ten week-old male offspring homozygous (non-functional class I MHC molecule) or heterozygous (functional class I MHC molecule) for beta 2-microglobulin knock-out gene did not differ in the following measures of bone turnover: femur length, dry and ash weight and calcium content, serum calcium concentration and alkaline phosphatase activity, total vertebral tissue area, trabecular bone volume, osteid surface, osteoclast surface and mineral apposition rate. These data indicate that the bone turnover in beta 2-microglobulin-deficient mice is appropriate for the stage of their skeletal maturation.

Animals↗

PubMed1991

The influence of plant growth regulators on callus induction in pumpkin (Cucurbita pepo L.) hairy roots.

Following in vitro infection with Agrobacterium rhizogenes wild strain (mannopine, 8196) and two A. tumefaciens transconjugant strains (C58C1 pArA4abc and C58C1 pArA4b) transformed (hairy) roots were induced in pumpkin (C. pepo L.) cotyledons. The presence of pRi T-DNA in pumpkin long-term hairy root cultures was determined by Southern hybridization. The influence of plant growth regulators on callus induction in root explants from hairy root lines, which differed mutually in morphology and growth rate, was tested by the addition of growth regulators to basal nutrient medium; while 2.4-D inhibited root proliferation in all hairy root lines tested, callus induction depended both on plant growth regulators and the root line.

Cell Differentiation↗