Signaling by way of type IB and II bone morphogenetic protein receptors regulates bone formation in otospongiosis.
OBJECTIVE
The main goal of this study was to perform an immunohistologic analysis of bone morphogenetic protein receptors (BMPR) in otospongiosis.


BACKGROUND
BMP-2, -4, and -7 play an essential role in bone formation and repair. They do so as well in otosclerosis. It has been shown that these BMPs are traceable in osteocytes and osteoclasts in the active phase of otosclerosis (otospongiosis). The role of the different BMP receptors in otosclerotic bone transformation has not been previously analyzed.


METHODS
The posterior parts of the stapes footplates, collected during partial stapedectomies in 35 patients with clinical otosclerosis, were analyzed for histologic otosclerotic lesions after hematoxylin staining. Immunohistochemical analysis was performed using polyclonal immunoglobulin G antibodies for BMPR-IA, -IB, and -II, as well as biotinylated secondary antibodies, avidin-biotin-peroxidase complex reaction, and alkaline phosphatase staining with nitroblue-tetrazolium-chloride.


RESULTS
Seventeen of 35 (49%) specimens contained otosclerosis, but only 5 of these exhibited an otospongiotic phase. The abundant osteoblasts and osteoclasts in these cases showed distinct immunochemical staining for BMP-2, -4, and -7. In two cases, there could also be found an immense positive staining for BMPR-IB and modest staining for BMPR-II, whereas BMPR-1A always remained negative.


CONCLUSIONS
It was demonstrated for the first time that in otospongiosis, the actions of the BMPs are mediated through BMPR-IB and BMPR-II. To determine this role in detail, further investigations, especially for the phosphorylated Smad proteins within the BMP dependent mediator cascade, will be necessary.
Lehnerdt
Goetz
G
Department of Otorhinolaryngology, University of Duisburg-Essen, Essen, Germany. goetz.lehnerdt@uni-due.de
Metz
Klaus Alfred
KA
Trellakis
Sokratis
S
Jahnke
Klaus
K
Neumann
Andreas
A
D000328:Adult; D052004:Bone Morphogenetic Protein Receptors / Q000378:metabolism*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D010012:Osteogenesis / Q000502:physiology*; D010040:Otosclerosis / Q000378:metabolism* / Q000503:physiopathology*; D015398:Signal Transduction; D013194:Staining and Labeling
D052004:Bone Morphogenetic Protein Receptors