This investigation was established because there had been no indications that allowed for the prediction of which patients would undergo early physeal arrest and which ones would not. It was unknown which signaling pathways became altered and caused changes following a traumatic injury about the physis that resulted in physeal arrest.
The purpose of this investigation was to use samples of both normal and damaged physes to analyze the histology and gene expression to try and determine which signaling pathways and cellular events result in physeal arrest. These analyses will provide both pathological information regarding physeal arrest and advance the information available regarding the possible preventative measures that may be taken to minimize the risk of this complication post-injury.
Throughout the course of this investigation, a system was established to safely and securely transport the specimens that were obtained during the epiphysiodesis procedure from the hospital to the laboratory. These samples, of both normal and damaged physes, were then prepared for histological analysis and sectioning. In total, 17 physes have been analyzed from 8 patients in total.
The results of the histological analyses revealed that the damaged physes showed alterations in the growth plate structure. Some of the damaged physes showed replacement of the cartilage (growth plate) with bone, fibrous tissues, and extensively disorganized cartilage masses. Some of the physes showed a sequential histological change which represented a possible pathway leading from the initial physis injury resulting in the loss of only the hypertrophic zone to physeal arrest resulting in disorganized resting zone of the entire growth plate. In addition to the histological findings, RNA was extracted from the dissected cartilaginous portions of the physes and the condition of the RNA was determined.
Overall, the outcomes of this investigation were successful in accomplishing the primary aim of the project. It was found that the cartilaginous portions of the damaged physis needed to be micro-dissected in order to appropriately analyze the gene expression of the physis due to the various amounts of bone present. The histological results of this study showed a promising start on the identification of the main factors that result in physeal arrest following a traumatic injury about the phsyis.
Future plans, presentations or publications as a result of this grant:
The future plans as a result of this grant are to continue to research the factors that are involved in physeal arrest. This will include performing immunohistochemistry analyses to examine the molecular changes that result in damaged physes. From the results of this investigation, an animal model has been established using mice to look at the condition of gymnast wrist and compare the histological and molecular signaling changes between the mouse physis and the human physis. If the animal model is successful, we will be applying for NIH funding to further investigate.
Presentation of parts of the results of this study will be presented at the ASBMR 2019 annual meeting.
A portion of the results of this study were submitted to ‘Osteoarthritis and Cartilage.’ The submitted manuscript was transferred for submission to a daughter journal, ‘Osteoarthritis and Cartilage Open.’