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Why babies need to move in the womb
Scientists have just discovered why babies need to move in the womb to develop strong bones and joints. It turns out there are some key molecular interactions that are stimulated by movement in order to guide embryonic cells and tissues to build a functional, strong, and malleable skeleton. If an embryo doesn't move, a vital signal can be lost or an inappropriate signal delivered, which can lead to development of brittle bones or abnormal joints.
Cells in the early embryo receive protein signals from other cells they come in contact with at various locations, directing them to contribute to new types of tissues. For example, our bones need to be strong and resilient to protect and support our body, whereas our articulating joints (knees, elbows, all joints) need to be covered in smooth, lubricated cartilage in order to move smoothly. As a result, cells in the early embryo are directed to become either bone or cartilage depending on location and time of arrival at the end of a bone.
Scientists understand many of the signals that direct cells to build bone, but know a lot less about cartilage. Currently, clinical treatment for joint degeneration is total replacement of the joint, improving the quality of life for many people but invasive surgery and not always a permanent solution. If we understood better how the embryo forms articular (joint) cartilage, we would be in a better position to regenerate cartilage from stem cells and improve treatment for joint injury and disease.
Professor in Zoology and lab director at Trinity College Dublin, Paula Murphy PhD, co-led such research just published in the international journal Development.
"The relative lack of understanding around how cartilage is directed presented an unfortunate knowledge gap because there are many painful, debilitating diseases that affect joints - like osteoarthritis - and because we also often injure our joints, which leads to them losing this protective cartilage cover.
Prior to Murphy's discovery, scientists had known that immobilized embryo movement reduced the ability of articular (joint) cells to form properly. In extreme cases, bones can fuse at a non-moving joint. However, researchers didn't know why. Now, isolating the Wnt and BMP signaling mechanisms underlying healthy movement during development provides insight into what types of signals need to be sent for a healthy joint.
The next step will be attempting to activate specific signals in order to generate stable joint cartilage. This will involve exposing cells to numerous combinations of biological signals to find the perfect cartilage recipe. Researchers will also build biophysical datasets about the exact movements needed in the hopes of diagnosing problems early. Clinicians may then be able to assist or compensate for natural signal exchange through movements they define. It could, for example, inform physiotherapeutic regimes that might alleviate joint damage.
Dynamic mechanical loading of synovial joints is necessary for normal joint development, as evidenced in certain clinical conditions, congenital disorders and animal models where dynamic muscle contractions are reduced or absent. Although the importance of mechanical forces on joint development is unequivocal, little is known about the molecular mechanisms involved. Here, using chick and mouse embryos, we observed that molecular changes in expression of multiple genes analyzed in the absence of mechanical stimulation are consistent across species. Our results suggest that abnormal joint development in immobilized embryos involves inappropriate regulation of Wnt and BMP signaling during definition of the emerging joint territories, i.e. reduced ß-catenin activation and concomitant upregulation of pSMAD1/5/8 signaling. Moreover, dynamic mechanical loading of the developing knee joint activates Smurf1 expression; our data suggest that Smurf1 insulates the joint region from pSMAD1/5/8 signaling and is essential for maintenance of joint progenitor cell fate.
Authors: Pratik Narendra Pratap Singh, Claire Shea, Shashank Kumar Sonker, Rebecca Rolfe, Ayan Ray, Sandeep Kumar, Pankaj Gupta, Paula Murphy, Amitabha Bandyopadhyay
Keywords: Wnt/BMP signalingArticular cartilageImmobilizationJoint developmentMuscle contractionMusclelessy.
The work is the result of a collaboration between Professor Murphy's research group in the School of Natural Sciences at Trinity, which focuses on the importance of embryo movement, and a group in the Indian Institute of Technology, Kanpur, led by Amitabha Bandyopadhyay. The collaboration was initiated with seed funding from Trinity's Faculty of Engineering, Mathematics and Science India Scheme, and the Trinity SFI ISCA India Programme. It was also later supported by a grant from the Indian Ministry.
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Mouse and chick fetal 3-D images reveal skeletal formation in utero. Along with gene expression,
these images help scientists visualize developing cartilage and associated joint movement.
Image credit: Professor Paula Murphy, Trinity College Dublin.