EFFECT OF STRONTIUM TREATMENT ON HUMAN PRIMARY OSTEOBLASTS. HYDROXYAPATITE: A DRUG DELIVERY SYSTEM?
Résumé
Objectives: Strontium is known to induce a positive bone balance but its specific pathway is still unknown. The purpose of this study is to test if Srsubstituted sol-gel HA could keep the osteogenic properties of strontium and so could enhance osteoformation, and if a specific pathway could be involved in that effect. Materials and Methods: Primary osteoblastic cells obtained from bone explants were used to study their proliferation when HA, Sr-substituted HA (HA5%), and Strontium chloride (5 x 10-5M ClSr2) were added to the culture medium at 3 culture times: 7, 14 and 21 days. PCR arrays and Cytokine Antibody Arrays were performed to detect differences in the RNA production and cytokines production. Non parametric stratified permutation tests were performed to check the significance of difference observed. p=0.05 level was used. Results: Proliferation: Strontium demonstrated a statistically significant increase of the osteoblastic cells replication without any changes in cells viability. Real time PCR demonstrated that osteoblastic cells were influenced by strontium which gave them an osteogenetic phenotype and modifications in expression of SMADs and TGFβ Receptors 1 and 2 tend to prove that strontium influences the TGFβ pathways. Osteoblasts produced 20 of the 42 cytokines that arrays could detect. Few showed differences in their expression after strontium treatment. GRO and MCP-1 production were modified in the osteogenic way. Conclusions: Strontium showed a high capacity to influence the bone balance to the osteogenesis by increasing the expression of constitutive proteins of bone RNAs and downregulating factors implicated in the initiation of osteoclastogenisis or the recruitment of osteoclasts. Those properties were kept when it was incorporated in sol-gel HA and the TGFβ pathway could be involved. In that way, HA acts as a drug delivery system.