X-linked hypophosphataemia (XLH) is the most common form of inherited rickets that leads to deformities in the lower limbs, poor tooth and skeletal mineralization, and disproportionate short stature in children. In adults, it is often complicated by enthesopathy, an abnormal mineralization of the tendon-bone attachment. Enthesopathy causes pain and stiffness in affected joints, particularly in the knee, hip, and ankle joints. Enthesopathy is reported as one of the most debilitating symptoms in XLH patients. Previous studies showed that entheses from mice with XLH (Hyp) are characterized by enhanced Bone morphogenic protein (BMP) and Indian hedgehog (IHH) signaling. This study aims to investigate the role of GDF5 in the development of enthesopathy in the Hyp mice. The study has two specific aims: (1) to determine if deleting GDF5 in enthesis (scleraxis-expressing (Scx+)) cells affects BMP/IHH signaling in entheses and (2) to determine if deleting GDF5 in Scx+ cells of Hyp mice attenuates XLH enthesopathy. The study hopes to gain a better understanding of role of GDF5 in enthesis maturation and XLH enthesopathy development. This study finds that deleting GDF5 in wild-type mice does not change normal enthesis maturation. However, deleting GDF5 in Hyp mice attenuates enthesopathy as indicated by decreased BMP/IHH signaling in Hyp entheses. / 2026-03-19T00:00:00Z
| Identifer | oai:union.ndltd.org:bu.edu/oai:open.bu.edu:2144/48443 |
| Date | 19 March 2024 |
| Creators | Sorsby, Melissa |
| Contributors | Bragdon, Beth, Liu, Eva |
| Source Sets | Boston University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
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