Expression of bone morphogenetic protein 2, 4, 5, and 7 correlates with histological activity of otosclerotic foci

Abstract

Active otosclerosis (n = 39) was characterized by increased expression of BMP2, 4, 5, and 7. Inactive cases of otosclerosis (n = 12) were characterized by negative immunoreaction for BMPs. Non-otosclerotic stapes specimens (n = 16) and negative controls (n = 41) showed negligible BMP expression. The BMP expression pattern showed a strong correlation with the histological activity of otosclerosis.

Identification of Target Proteins Involved in Cochlear Otosclerosis

“…Furthermore, a recent case-controlled genetic study revealed that the TGFß1 polymorphism c. – 509C > provides a disease- causing effect in the Indian population, and mRNA analysis demonstrated increased expression of TGFß1 in ankylotic stapes specimens compared with controls. 39 Mechanisms involved in cochlear extension of the otosclerotic lesion are still unclear, but the implication of TGFß1 is supported by the present proteomic data and confirmed by our immunostaining results as well. No previous studies of which we are aware have shown the implication of TGFß1 in the cochlear otosclerotic lesion with SL hyalinization.…”

“…37 Evidence of a possible association of a TGFß1 polymorphism and otosclerosis involving stapes ankylosis has been shown 38 with the implication of bone morphogenetic proteins (BMP) 2, 4, 5, and 7, which are members of the TGFß superfamily. 29, 39 BMP 5 and 7 may play a predominant role in the active part of the stapedial involvement with otosclerosis, its pattern evolving with the disease. 39 Although otosclerotic stapes ankylosis can be limited to the oval window area, without any cochlear extension, these lesions likely share similar pathophysiology as the present study suggests.…”

“…29, 39 BMP 5 and 7 may play a predominant role in the active part of the stapedial involvement with otosclerosis, its pattern evolving with the disease. 39 Although otosclerotic stapes ankylosis can be limited to the oval window area, without any cochlear extension, these lesions likely share similar pathophysiology as the present study suggests. Furthermore, a recent case-controlled genetic study revealed that the TGFß1 polymorphism c. – 509C > provides a disease- causing effect in the Indian population, and mRNA analysis demonstrated increased expression of TGFß1 in ankylotic stapes specimens compared with controls.…”

Novel NOG mutation in Japanese patients with stapes ankylosis with broad thumbs and toes

“…Expression of BMP14 was recognized in the annular stapedial ligament, and absence of BMP14 expression in the middle ear ossicles was suggested to lead to failure of inossicular joint formation (Hwang and Wu, 2008). Active otosclerosis was characterized by increased expression of BMP2, 4, 5, and 7 (Csomor et al, 2012), and normal middle ear development in mice showed expression of not only BMP14 but also of BMP2, 4, and 7 (Hwang and Wu, 2008). Taken together, SABTT phenotype is suggested to be associated with modulated BMP14 signaling and modulated BMP2, 4, 5, and 7 signaling by mutated NOG protein.…”

The Putative Role of Measles Virus in the Pathogenesis of Otosclerosis

“…Lehnerdt et al have performed immunohistochemical analysis of BMPs and BMP receptors in otosclerotic stapes footplates [ 57 , 58 ]. Signifi cantly increased BMP2, BMP4, and BMP7 expression was demonstrated within the otosclerotic foci compared to normal and non-otosclerotic bone specimens [ 59 ]. Among BMP receptors, BMPR-1B and BMPR-2 showed increased immunoreactivity, whereas BMPR-1A always exerted negative reaction [ 57 , 58 ].…”