Periodic Reporting for period 2 - Grolaries (Cartilage progenitor cells for growth plate regeneration)
Periodo di rendicontazione: 2021-01-01 al 2021-12-31
(Aim 2-3) The following activities regarding with the study of GP dynamics and developing of new drugs,were performed at the University of Zurich in colaboration with the University of Oviedo:
Mice experiments on XLH animal model with potential drugs for XLH treatment
Cell culture experiments using potential drugs for XLH treatment
Collection and analysis of data
Writing a manuscript to Bone Research: "Blocking FGF23 function with modified C-terminal FGF23 peptides as a novel therapy for X-linked hypophosphatemia rickets"
Preliminary data shows that C-terminal and N-terminal FGF23 peptides are able to improve tibia length and growth plate structure in PHEX mice compared with control PHEX mice and higher value than the already published one cFGF23, rescuing in part the GP aberrations acting predominantly on the hypertrophic zone (HZ) (see table bellow) (Figure 1C and 1D).Our data indicate that treatment with the Nmod and Cmod peptides partially reversed part of the pathological symptoms of XLH. The corrections of the profound GP morphological abnormalities are independent of the degree of hipophophatemia and indicate a direct relationship between FGF23 and cartilage diferenciation. Thereby these drugs emerged as a promising new therapy to reduce the risk of bone deformities in XLH patients and regulate cartialage diferenciation, critical factor in other more prevalent diseases such as osteoarthitis. We also hypothesis that in order to improve bone quality normalization of FGF23 is not enaought and a normalization in the Pi levels should be approached.
We chose XLH as a model disease because despite being considered a rare disorder, is the most common hereditary rickets in the clinic. Even though the most relevant phenotypic characteristic is growth plate deformities that lead to growth impairment, to date the underlying mechanisms are not widely studied and most studies are carried out in adults and focus on bone metabolism. In the fallowing year we aim to better understanding the mechanism that operate in the GP and how FGF23 related therapies direct affect its development. The techniques developed in this project will allow to analyze the mechanisms and dynamics of the growth cartilage development and repair. The results of this study will therefore be easily transferable to the clinic and can be applied to other pathologies with a high socio-sanitary impact, such as joint osteoarthritis, where chondrocyte development and differentiation also play a relevant role. Likewise, the project will facilitate the research training of the group's pre-doctoral members and is laying the foundations for possible future projects.