ESPE Abstracts (2015) 84 P-3-1014

Altered Gene-Expression in Human Growth Plate Cartilage Tissue Exposed to Dexamethasone

Therése Cedervall, Farasat Zaman & Lars Sävendahl

Department of Women’s and Children’s Health, Karolinska Institute, Stockholm, Sweden

Background: Synthetic glucocorticoids (GCs) are widely used drugs but their suppression of growth in pediatric patients is a well-known problem. Different mechanisms have been suggested but we still do not know the sensitivity of human growth plate cartilage to GC treatment. Here in this study, we have investigated the direct effects of GC treatment on the expression of crucial genes in the growth plate, such as collagen-2A1, osterix (Osx), and transforming growth factor β1 (TGF-β).

Objective and hypotheses: Our aim was to study the expression pattern of collagen-2A1, Osx and TGF-beta in human growth plate cartilage when exposed to GCs.

Method: Biopsies of human growth plate cartilage from one boy (patient 1), pubertal stage GH; PH4 (Tanner), and one girl (patient 2), pubertal stage B2; PH2, were obtained at epiphyseal surgery. Sections of the cartilage were cultured and treated for 24 h with 10 uM dexamethasone, and snap-frozen in liquid nitrogen. RNA was extracted with Trizol® and qPCR was performed with primers for human collagen-2A1, Osx, and TGF β1.

Results: In patient 1, we found that dexamethasone suppressed collagen-2A1 expression by 88%, compared to control. Interestingly, dexamethasone also suppressed TGF-beta by 79%, compared to control. There was a slight increase in Osx expression in dexamethasone treated cartilage vs control. In patient 2, there were only marginally changes in the gene expressions between the control and GC-treated cartilage sections.

Conclusion: These data from rare growth plate tissue obtained from paediatric patients suggest that GCs can directly sensitize human growth plate chondrocytes and differentially regulate genes involved in chondrogenesis. We also observed that the tissues from the two patients responded differently when challenged to GCs. More observations are needed to confirm these results, which’ll help us to understand direct effects of GC therapy on bone growth.

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