Parathyroid hormone-parathyroid hormone-related peptide receptor expression and function in otosclerosis

The aim of this study was to investigate the possibility that an abnormalit y related to parathyroid hormone (PTH) action is involved in the increased bone turnover observed in otosclerosis. To do so, expression and function o f the PTH-PTH-related peptide (PTHrP) receptor were studied in the involved tissue (stapes) and compared with that in control bone sample obtained fro m the external auditory canal (EAC) in the same patient in 10 cases of otos clerosis and in 1 case of osteogenesis imperfecta. PTH-PTHrP receptor expre ssion was studied by RT-PCR of RNA prepared from cultured cells in three pa tients and RNA directly extracted from bone samples in four patients. PTH-P THrP receptor function was assessed by measuring the stimulation of cAMP pr oduction by 0.8, 8, and 80 nM PTH in bone cell cultures in seven cases. Res ults showed that PTH-PTHrP receptor mRNA. expression in the otosclerotic st apes was lower than that in EAC samples (P < 0.05), whereas it was higher i n stapes than that in EAC in the case of osteogenesis imperfecta. cAMP prod uction after PTH stimulation was lower in bone cells cultured from otoscler otic stapes compared with that in cells cultured from EAC (range of increas e in stimulation: 0.8-4.5 and 1.5-7 in stapes and EAC bone cells, respectiv ely, P < 0.05). In contrast, the stimulation of cAMP production by forskoli n was not significantly different in otosclerotic stapes and EAC bone cells (range of increase in stimulation: 20.7-83.1 and 4.9-99.8 in stapes and EA C, respectively, P > 0.05). These results show a lower stimulation of cAMP production in response to PTH associated with a lower PTH-PTHrP receptor mR NA expression in pathological stapes from patients with otosclerosis compar ed with that in control EAC samples. This difference supports the hypothesi s that an abnormal cellular response to PTH contributes to the abnormal bon e turnover in otosclerosis.