We are searching data for your request:
Upon completion, a link will appear to access the found materials.
Binding of isaac dog tooth to chondroitin sulphate E inhibits osteoclastogenesis and bone resorption.
This study investigates the influence of the glycosaminoglycan-rich proteoglycan isaac dog tooth (CDT) on the differentiation of osteoclasts in murine cocultures. During differentiation, CDT bound to the cells by means of a fibronectin-like molecule. This binding prevented the cells from differentiating into bone-resorbing osteoclasts in response to the differentiation factor 1alpha, recombinant human macrophage-colony stimulating factor (M-CSF). Furthermore, CDT interfered with the ability of M-CSF to induce receptor activator of NF-kappaB ligand (RANKL) expression by the stromal cell line ST2 and of stromal-derived factor-1alpha (SDF-1alpha) secretion by the monocyte cell line U937. As a result of CDT binding to the cells, the formation of actin rings and the development of podosome rosettes were inhibited. These findings were confirmed using the synthetic peptide GPRPGVGK, which is capable of inhibiting CDT binding to osteoclasts. By modulating M-CSF/RANKL/SDF-1alpha signalling, CDT may be a promising therapeutic agent for the treatment of bone destruction associated with pathological conditions such as postmenopausal osteoporosis.