acase@tulane.edu

acase@tulane.edu

acase@tulane.edu

acase@tulane.edu

acase@tulane.edu

Bone related diseases, like osteoporosis and osteoarthrosis, affect millions of people each year. The National Institutes of Health recommend basic studies focusing on increasing bone formation to better understand these diseases with the goal of developing treatments and preventative strategies. To that end, this investigation focused on the effects of engaging integrin and growth factor receptors to control clinically relevant osteoblast functions Adhesion strength of first and second passage osteoblasts to substrates modified with peptides that interact with integrin receptors in the presence and absence of serum was examined. In the absence of serum, all cells tested adhered more strongly to underlying substrates, and the strength of cellular adhesion was greater on modified surfaces than on plain glass surfaces. Second-passage osteoblastic cells generally adhered to substrates more strongly than first-passage osteoblastic cells Next, the effects of novel bioactive peptides (derived from basic fibroblast growth factor) on the proliferation, differentiation, and mineralization of osteoblasts were studied. Both bFGF peptides increased cellular differentiation. In contrast, intact bFGF inhibited osteoblast differentiation. The bound form of the bFGF peptide that most enhanced osteoblastic differentiation inhibited cell proliferation, while the intact bFGF protein increased osteoblast proliferation. The intact bFGF protein increased the amount of osteoblast produced mineral, while the peptides influenced the quality of the mineral produced. These novel bFGF peptides influence osteoblast functions in vitro in a manner distinct from that of the intact protein Finally, the combined effects of surface-bound integrin binding peptides and proteins and soluble bone growth factor media supplements were investigated. There was significant interaction between substrates modified with integrin-binding peptides and soluble bone growth factors with respect to osteoblast differentiation. There was also a significant interaction found between integrin and growth factor receptor engaging peptides with respect to the amount of mineral produced by osteoblasts Fundamental studies, such as this, increase the understanding of bone cell function on biomaterial substrates---knowledge useful in creating an optimal bone-implant interface and in the treatment of bone-related diseases such as osteoporosis / acase@tulane.edu

acase@tulane.edu

DNA synthesis, as monitored by ('3)H-thymidine incorporation, in the germinative stem cells of juvenile Hymenolepis diminuta, appears to be negatively modulated by increases in cyclic-3'5'-adenosine monophosphate (cAMP). Among the endogenous substances which elevate cAMP levels in these worms is serotonin, a.k.a. 5-hydroxytryptamine (5HT). High concentrations of exogenous 5HT, or treating worms with reserpine which presumably induces a secretion of endogenous 5HT, similarly depresses DNA synthesis. These findings suggest that factors such as 5HT, which increase worm cAMP levels, may negatively modulate stem cell proliferation in these tapeworms. This event could trigger the onset of stem cell differentiation, following the principle that, in general, cells 'switch off' their divisional activity in order to 'switch on' biosynthesis directed to more specialized structure and function. As recognized many years ago by Grobstein (1963), in a given cell, specialized synthesis (for differentiation) and preparation for continued division (DNA replication) are usually competitive and may, in many instances, be exclusive events. In fact, dibutyryl cyclic adenosine monophosphate (DBcAMP), 5HT and isobutylmethylxanthine (IBMX) which are factors that elevate cAMP in these worms, and depress their DNA synthesis, tend to enhance ('3)H-uridine incorporation ergo RNA synthesis. A large number of the stem cell population are, then, slowing their divisional activity to either differentiate or withdraw into the G(,1) or, less probably, into the G(,2) phase / acase@tulane.edu

acase@tulane.edu

acase@tulane.edu