2023-09-07 08:04:46
The inner ear located at the thickest part of the temporal bone is composed of 2 main elements:
the bony labyrinth protects the auditory apparatus and in particular the 2nd element, the membranous labyrinth, the membranous labyrinth ensuring the functions of hearing and balance.
Cholesteatoma is characterized by the presence of skin cells inside the cavities of the middle ear, made up of 3 small bones that transmit vibrations to the inner ear. Cholesteatomas thus appear as small cysts in the ear made up of skin, collagen fibers, skin cells, fibroblasts, keratin and dead tissue. Many theories have been put forward on how these cholesteatomas can cause bone erosion, including the activation of cells responsible for the breakdown of minerals and bone matrix (osteoclasts), the presence of inflammatory markers and d enzymes, and the accumulation and pressure of dead cells and tissues in the ear. However, until this study, the exact mechanism of cholesteatoma development was poorly understood.
Additionally, while cholesteatoma can still reappear or recur even following surgical removal, “it is important to know what actually causes it to develop,” says lead author, researcher Kotaro Shimizu.
The study: To answer the question, the team analyzed biopsies of human cholesteatoma taken from patients. By single-cell RNA sequencing, the researchers were able to identify the cells responsible for triggering bone erosion: osteoclastogenic fibroblasts. The analysis deciphers precisely how these fibroblasts express an abundant quantity of activin A, a molecule which regulates various physiological functions of the body and which causes bone erosion.
The key role of activin A, a protein expressed by bone fibroblasts: specifically, Japanese researchers describe the relationship between activin A, a protein expressed by fibroblasts and bone erosion, in cholesteatoma. In other words, in cholesteatoma,
fibroblasts expressing activin A under the impulse of pro-inflammatory cytokines secreted by infiltrating macrophages, trigger and maintain osteoclastogenesis or overproduction of osteoclasts,
cells responsible for bone resorption. During this process, activin A works in conjunction with another protein, RANKL to promote osteoclastogenesis.
The promises of a therapy that targets activin A: By deciphering these processes involved in cholesteatoma, the team is laying the foundations for new therapies. It also brings hope for therapy, demonstrating that targeting activin A is promising in the management of cholesteatomas. The only effective treatment for cholesteatomas currently in clinical practice is surgical removal.
However, the discovery of how a cholesteatoma can cause bone erosion offers new hope for the first-line management of cholesteatomas.
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#CHOLESTEATOMA #bone #loss #ear
