Expression of growth differentiation factor-5 and bone morphogenic protein-7 in intraocular osseous metaplasia

Abstract

Background/aims: Intraocular bone is seen in a wide spectrum of ocular disorders. The pathogenetic mechanisms of bone formation in the eye are unclear. Growth differentiation factor-5 (GDF-5), bone morphogenic protein-7 (BMP-7), and transforming growth factor beta-1 (TGF b1) are multifunctional cytokines that have important roles in bone formation. Immunohistochemistry was used to localise GDF-5, BMP-7, and TGF b1 in the human eye to determine their role in intraocular bone formation. Methods: Paraffin embedded sections from human eyes included fetal eyes (n = 5), normal adult eyes (n = 4), eyes with osseous metaplasia (n = 8), and eyes with focal fibrous metaplasia of the retinal pigment epithelium (RPE) without osseous metaplasia (n = 2). Immunohistochemistry was performed using indirect immunofluorescence with antibodies to GDF-5, BMP-7, and TGF b1. The staining intensity was evaluated semiquantitatively in the RPE, retina, ciliary epithelium, and cornea; and analysed statistically. Results: When compared with normal adult eyes, which showed no RPE immunoreactivity, the RPE metaplasia surrounding areas of osseous metaplasia showed mild GDF-5 and moderate BMP-7 (p = 0.004) intracytoplasmic immunoreactivity. In contrast, trace GDF-5 and mild BMP-7 staining was seen in zones of RPE fibrous metaplasia in areas not associated with osseous metaplasia. Mild intracytoplasmic TGF b1 expression was seen in the RPE metaplasia surrounding the bone when compared with adult eyes. Both fetal and adult eyes showed trace to mild GDF-5 and BMP-7 labelling of the non-pigmented ciliary epithelium which was increased in the eyes with osseous metaplasia. In eyes with osseous metaplasia, a significant decrease in GDF-5 and BMP-7 labelling was noted in fetal keratocytes (p = 0.0159 for both antibodies) when compared to adult eyes. Also, a significant decrease in BMP-7 labelling was seen in keratocytes in eyes with osseous metaplasia (p = 0.0162). Conclusions: The increase in GDF-5, BMP-7, and TGF b1 immunoreactivity in zones of RPE metaplasia in eyes with osseous metaplasia suggests that these proteins have an important role in intraocular ectopic bone formation.

Gross, histologic, and computed tomographic characterization of nonpathological intrascleral cartilage and bone in the domestic goat (Capra aegagrus hircus)

“…There are a number of mechanisms by which bone and/or cartilage form within ocular structures; these include (i) congenital ectopic (choristomatous) bone/cartilage formation, (ii) osseous metaplasia as a pathologic response (e.g., post‐traumatic or intratumoral), (iii) an adaptive response to physiologic stressors within an individual's environment, or (iv) as a normal developmental finding within all or the vast majority of individuals within a species. Given the high prevalence of affected animals, and the lack of other ectopic tissues, it seems unlikely that our findings represented choristomatous cartilage or bone formation.…”

Cholesterol granuloma of the anterior mediastinum with osseous metaplasia

“…9,15 It is theorized to be the result of pluripotent cell, mesenchymal cell, and fibroblastic differentiation into osteoblasts due to stimulation by pro-inflammatory cytokines such as interleukins and transforming-growth-factor-beta, and bone morphogenetic proteins. 16–18 …”

Heterotopic ossification after the use of commercially available recombinant human bone morphogenetic proteins in four patients

“…Discussion HO can occur in many sites. [22][23][24][25][26][27] While the mechanisms associated with many cases of HO remain elusive, one hypothesis is that it is associated with an inflammatory response resulting from the elaboration of specific biochemical mediators and growth factors, which leads to the recruitment of mesenchymal stem cells capable of differentiating into cartilage and/or bones. 28,29 The role of an inflammatory response as a contributing factor in the development of HO can be inferred from the apparent prophylactic effects of indometacin in the prevention of HO around the pelvis after hip surgery, acetabular fracture, [30][31][32] and in the spine after injury to the spinal cord.…”