Study on normal and otosclerotic bone cell cultures: An advance in understanding the pathogenesis of otosclerosis

Abstract

The authors first reviewed the main theories concerning the pathogenesis of otoselerosis and studied the morphologic and functional characteristics of cell cultures derived from normal and otosclerotic bones. Light transmission and scanning electron microscopy did not permit definite identification of the cultured cells as predominantly osteoblasts, nor did these techniques show significant differences between cultured ceils derived from normal and pathologic bone. Functional tests of the cell cultures proved more interesting. First, the bony nature of the cultured cells was demonstrated by studying the intracellular 45Ca++ uptake after stimulation with calcitonin and dybutryl-cAMP. Second, cell cultures derived from otosclerotic bone behaved differently from those derived from normal bone. Their peak uptake of calcium appeared later, and post-stimulatory values were higher, suggesting that cells derived from otosclerotic bone store a greater quantity of 4SCa ++. Furthermore, after stimulation with calcitonin and propranolol, we observed an inhibition of the calcium uptake and decreased intracellular cAMP levels in normat bone cell cultures. In contrast, the cell cultures derived from otosclerotic bone exhibited an initial inhibition of calcium absorption followed by massive calcium penetration.The response of adenylate cyclase to the action of Mg + § Ca + +, and F-ions was evaluated in cultures derived from normal bone, otosclerotic bone, and normal skin fibroblasts. The resulting data show that activation due to Mg + § is much lower in cultured cells derived from otosclerotic bone than in those from either normal bone or skin fibroblasts. No significant differences were found after .Ca ++ inhibition in any of the cell cultures. Moreover, in cell cultures derived from normal bone, F-ions induced a strong activation that was lower than the levels observed in cultures of otosclerotic bone or in normal fibroblasts. We hypothesize that an alteration at the calcitonin receptor site is responsible for the difference in calcium uptake and cAMP levels observed in the cells derived from otosclerotic bone as compared to those cultured from normal cells.

Functional assay, expression of growth factors and proteins modulating bone-arrangement in human osteoblasts seeded on an anorganic bovine bone biomaterial

“…These hormones have specific receptors in the plasma membranes of bone cells (Lerner and Lundberg, 2002). The binding of CT to its receptors (Lerner and Person, 2008) is inhibited by blockers of β-adrenergic receptors, such as propanolol (Maurizi et al, 1988;Togari et al, 1997). Several papers in the literature have reported that primary cultures of human osteoblast-like cells expressed a CT receptor-like receptor (CLR) (Villa et al, 2006) and as other osteoblastlike cells (UMR-106) possessed CT-and PTH receptors (Yamaguchi et al, 1987).…”