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[In vitro effects of growth hormone on osteoclastic activity: clinical applications]
A V Rousselle1, C Damiens, J Guicheux
1Laboratoire de Physiopathologie de la Résorption Osseuse et Mécanismes de cicatrisation, EE-99/01, 1, place Alexis Ricordeau, 44042 Nantes Cedex 1, France.
Purpose Of The Study:
This study was designed to investigate the in vitro effects of human growth hormone (hGH) on osteoclastic resorption in a nonfractionated rabbit bone cell model.
Material And Methods:
Rabbit bone cells were cultured on dentine slices in the presence of parathyroid hormone and vitamin D3. The percentage of dentine slice surface resorbed, number of lacunae per surface unit and mean area of lacunae were compared between cell cultures grown in the presence of graded concentrations of hGH and human insulin-like growth factor-1 (hIGF-1) and controls.
Results:
After 4 days of culture, rabbit bone cells cultured on dentine slices in the presence of hGH and hIGF-1 showed significantly stimulated osteoclastic resorption activity. When neutralizing anti-hIGF-1 anti-serum (4 microg/l) was added to the starting culture, the stimulatory effects of hIGF-1 and hGH on osteoclastic resorption activity were totally abolished.
Discussion:
These findings indicate that the effects of hGH stimulation on osteoclastic resorption in vitro are mediated via local hIGF-1 secretion by stromal cells such as osteoblasts. Proteases appear to play a role in the degradation of the organic matrix. Our experiments show that hIGF-1 and hGH stimulate the production of matrix metalloproteinases MMP-9 and MMP-2. Similar to the resorption activity, hGH stimulates protease activity via stromal cell production of hIGF-1.
Conclusion:
This study suggests that natural or synthetic MMP inhibitor modulation of protease activity could reduce the degradation of the organic matrix and then prevent, for example, inflammatory reactions subsequent to prosthetic loosening.