title: Signaling by way of type IB and II bone morphogenetic protein receptors regulates bone formation in otospongiosis.
abstract: 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.
authors.affiliation: Department of Otorhinolaryngology, University of Duisburg-Essen, Essen, Germany. goetz.lehnerdt@uni-due.de
authors.forename: Goetz
authors.initials: G
authors.lastname: Lehnerdt
authors.forename: Klaus Alfred
authors.initials: KA
authors.lastname: Metz
authors.forename: Sokratis
authors.initials: S
authors.lastname: Trellakis
authors.forename: Klaus
authors.initials: K
authors.lastname: Jahnke
authors.forename: Andreas
authors.initials: A
authors.lastname: Neumann
mesh_terms: 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
chemical_list: D052004:Bone Morphogenetic Protein Receptors