Vol. 277, Issue 6, E1005-E1012, December 1999
Parathyroid hormone-parathyroid hormone-related peptide
receptor expression and function in otosclerosis
Alexis Bozorg
Grayeli1,
Olivier
Sterkers1,2,
Pierre
Roulleau3,
Pierre
Elbaz4,
Evelyne
Ferrary1, and
Caroline
Silve1
1 Institut National de la
Santé et de la Recherche Médicale Unité 426,
Faculté Xavier Bichat, Université Paris 7, 75018 Paris;
2 Service d'Otorhinolaryngologie,
Hôpital Beaujon, Assistance Publique-Hôpitau de Paris,
92118 Clichy; 3 Service
d'Otorhinolaryngologie Department, Hôpital Necker, Enfants
Malades, Assistance Publique-Hôpitaux de Paris, 75015 Paris; and
4 Service d'Otorhinolaryngologie,
Fondation Adolphe de Rothschild, 75012 Paris,
France
The aim of this
study was to investigate the possibility that an abnormality related to
parathyroid hormone (PTH) action is involved in the increased bone
turnover observed in otosclerosis. To do so, expression and function of
the PTH-PTH-related peptide (PTHrP) receptor were studied in the
involved tissue (stapes) and compared with that in control bone sample
obtained from the external auditory canal (EAC) in the same patient in
10 cases of otosclerosis and in 1 case of osteogenesis imperfecta.
PTH-PTHrP receptor expression was studied by RT-PCR of RNA prepared
from cultured cells in three patients and RNA directly extracted from bone samples in four patients. PTH-PTHrP receptor function was assessed
by measuring the stimulation of cAMP production by 0.8, 8, and 80 nM
PTH in bone cell cultures in seven cases. Results showed that PTH-PTHrP
receptor mRNA expression in the otosclerotic stapes was lower than that
in EAC samples (P < 0.05), whereas it was higher in stapes than that in EAC in the case of osteogenesis imperfecta. cAMP production after PTH stimulation was lower in bone
cells cultured from otosclerotic stapes compared with that in cells cultured from EAC (range of increase in stimulation: 0.8-4.5 and 1.5-7 in stapes and EAC bone cells, respectively, P < 0.05). In contrast, the
stimulation of cAMP production by forskolin 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 EAC,
respectively, P > 0.05). These results show a lower stimulation of cAMP
production in response to PTH associated with a lower PTH-PTHrP
receptor mRNA expression in pathological stapes from patients with
otosclerosis compared with that in control EAC samples. This difference
supports the hypothesis that an abnormal cellular response to PTH
contributes to the abnormal bone turnover in otosclerosis.
bone turnover; middle ear; stapes
