Key regulator of bone development revealed

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Key regulator of bone development revealed

The investigators at Penn State University discovered the knocked out the Speckle-type POZ Protein (Spop) in the mouse and identified its impact on the bone development. The role of Spop during bone development and a new potential target for the diagnosis and treatment of bone diseases like osteoporosis appeared online in the journal Proceedings of the National Academy of Sciences on December 5.

According to Aimin Liu, associate professor of biology at Penn State and the corresponding author of the study, “the Spop protein is involved in Hedgehog signaling — a well-studied cell-to-cell communication pathway that plays multiple roles during development. Former studies in cell culture have revealed that Spop negatively regulates or ‘turns down’ Hedgehog signaling. However, according to the presented study, Spop positively regulates the pathway downstream of a member of the Hedgehog family- a protein called Indian Hedgehog, during the bone development. This novel understanding further clarified the knowledge of the genetic basis of bone development and could open new platforms to study bone disease.

The Indian Hedgehog (Ihh) plays a crucial part in the bone development. It occurs near the top of a hierarchical cascade of genes that program cells to create cartilage and bone. The Ihh controls gene expression by modulating the activity of the transcription factors and proteins that direct the expression of other genes called Gli2 and Gli3. The activator of the gene expression is Gli2, while Gli3 mostly functions to repress the expression of the gene.

Hongchen Cai, a graduate student at Penn State and an author of the paper said that “previous studies led to a hypothesis that a loss of Spop function would increase the Hedgehog signaling because the Gli activators were no longer being degraded. We were surprised to see in our study the repressor of gene expression, Gli3, built up in developing bone, but not the activator of gene expression, Gli2. This imbalance led to an overall decrease in Hedgehog signaling”.

The investigators knocked the gene out, particularly in the limb to efficiently understand the role of Spop in bone development. The limbs that lacked Spop had less dense bone, imitating osteopenia — a human condition marked by low bone density, but not as extreme as osteoporosis. Shorter than normal fingers and toes were observed in the limbs. The effects of losing Spop could be alleviated by simultaneously reducing the amount of Gli3 in the limbs as depicted by the investigators.

Source:

Pennsylvania State University

Link to the source:

http://www.comfortfinders.com/osteoporosis-news/osteoporosis-research-news-key-regulator-bone-development-identified/

The original title of the article:

Osteoporosis Research News: Key regulator of bone development identified

Authors

D.C. Penoni et. al

SearchTags: 
Exploratory, Osteoporosis, Bones
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