Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Pichler, K.
Mechanisms and effects of trauma on pediatric growth
[ Dissertation ] Medical University of Graz; 2013. pp. 92
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- Autor*innen der Med Uni Graz:
- Pichler Karin
- Betreuer*innen:
- Leithner Andreas
- Marth Egon
- Weinberg Annelie-Martina
- Altmetrics:
- Abstract:
- The growth plate at each end of long bones is a unique feature of a child¿s bone. It is the site of enchondral ossification, orchestrating longitudinal bone growth in a highly complex process. Injuries to the growth plate, especially trauma and stress related injuries, can severely impair this process leading to bone growth disturbances. The first part of this thesis deales with the proliferation and differentiation behaviour of growth plate chondro-progenitorcells in the initial inflammatory phase of growth plate injury response. In this early phase of injury response growth plate chondro-progenitorcells differentiate towards hypertrophy, while proliferation remains unaffected and chondrogenesis and ossification are inhibited. This might be the first step towards an unwanted pre-mature ossification of the growth plate. Treatment strategies to prevent it should start immediately after a trauma occurs. Next the expression of MMPs in human growth plate chondrocytes in response to various loading durations and intensities was studied, aiming to identify possible molecular mechanisms involved in the development of overuse injuries in children. Overuse injuries are an emerging clinical problem given the fact that greater numbers of children participate in sports at earlier ages, with increased levels of training and competition. MMPs are responsible for extracellular matrix remodeling and regulation of angiogenesis in the growth plate, two processes crucial for appropriate enchondral ossification. This work showed that MMP expression decreased when human growth plate chondrocytes were exposed to physiologic loads, suggesting that under these conditions cells are in an anabolic state where matrix remodeling is limited and enchondral ossification can occur regularly. However, when chondrocytes were subjected to detrimental stress, expression of MMPs increased significantly. This indicates that detrimental stress on the growth plate leads to an accelerated degradation of extracellular matrix proteins and an increased vascularization of the growth plate. Such an increased growth plate turnover, especially the premature ingrowth of vessels into the growth plate might lead to a temporary mechanical tissue instability favoring overuse injuries. Interestingly an increased expression of MMPs was detected not only when detrimental stress was applied on the chondrocytes, but also when mechanical loading of mild intensity was applied for a longer period, i.e. 24 h. This is an interesting and novel finding, indicating that also physiologic loads can have detrimental effects on growth plate tissue when applied long enough. Based on this findings training programs for immature athletes should be rethought carefully. Training intensities should be adapted not to harm the growing body and regeneration intervals should be appropriate thus avoiding physiological loads from becoming detrimental. In the last part of this thesis the effect of a slow and a fast degrading magnesium based implant on human growth plate chondrocytes and osteoblasts was investigated. Magnesium based imlants are promising candidate implant materials for use in osteosynthesis. Their self-degrading properties would render a second surgical intervention for implant removal unnecessary. This would be desirable especially in pediatric patients, because surgery and the associated hospital stay means a major stress for them. I demonstrated that magnesium alloys for use in biodegradable implant application are well tolerated in osteoblasts and primary human growth plate chondrocytes. The slower degrading magnesium alloy showed a superior performance when compared to the faster degrading alloy. However, the slower degrading magnesium alloy contains the rare earth element yttrium, which raises concerns about using it in a degradable implant solution for children, as it is potentially neurotoxic. Further studies are needed to study its influence in detail.