Matrix metalloproteinases (MMPs), responsible
for extracellular matrix remodelling and angiogenesis, might play
a major role in the response of the growth plate to detrimental
loads that lead to overuse injuries in young athletes. In order
to test this hypothesis, human growth plate chondrocytes were subjected
to mechanical forces equal to either physiological loads, near detrimental
or detrimental loads for two hours. In addition, these cells were
exposed to physiological loads for up to 24 hours. Changes in the
expression of MMPs -2, -3 and -13 were investigated. We found that expression of MMPs in cultured human growth plate
chondrocytes increases in a linear manner with increased duration
and intensity of loading. We also showed for the first time that
physiological loads have the same effect on growth plate chondrocytes
over a long period of time as detrimental loads applied for a short
period. These findings confirm the involvement of MMPs in overuse injuries
in children. We suggest that training programmes for immature athletes
should be reconsidered in order to avoid detrimental stresses and
over-expression of MMPs in the growth plate, and especially to avoid
physiological loads becoming detrimental. Cite this article:
The role of heritable thrombophilic risk factors in the pathogenesis of the Perthes’ disease is controversial. The clinical and radiological findings of Perthes’ disease may be indistinguishable from those of Gaucher’s disease, and the most common Jewish N370S Gaucher mutation is threefold greater in patients with Perthes’ disease. Familial osteonecrosis of the femoral head is associated with variant mutations of collagen type II (COL2A1 mutations). We therefore studied the potential role of genetic thrombophilia and the Gaucher and COL2A1 mutations in children with Perthes’ disease. Genomic DNA of 119 children with radiologically-confirmed Perthes’ disease diagnosed between 1986 and 2005 was analysed for the thrombophilic polymorphisms Factor V Leiden, 677T-MTHFR and FIIG20210A. The results were compared with those of a group of 276 children without Perthes’ disease. DNA was also analysed for the Gaucher mutations N370S, G insertion (84GG), L444P, Intron 2 (IVS2+1G>
A) and R496H. Enzymic assays confirmed the Gaucher disease status. Collagen (COL2A1) mutations of the 12q13 gene were also analysed. The prevalence of thrombophilic markers was similar among the 119 patients with Perthes’ disease and the 276 control subjects. The prevalence of the Gaucher mutation was consistent with Israeli population carriership data and did not confirm an earlier-claimed association with Perthes’ disease. All 199 patients were negative for the studied COL2A1 mutations. We found no genetic association between Perthes’ disease and either Gaucher’s disease or COL2A1 mutations or increased genetic thrombophilia among our patients compared with the control group. A systematic review of case-control studies suggested that there was a positive association between Perthes’ disease and Factor V Leiden. The impact of this association upon the disease, although not consistent across the studies, remains unclear.
