Mesenchymal stem cell proliferation and mineralization but not osteogenic differentiation are strongly affected by extracellular pH

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• 作者：Riham Fliefel^a ; ^b ; ^c ; ^{Riham.Fliefel@med.uni-muenchen.de" class="auth_mail" title="E-mail the corresponding author} ; Cvetan Popov^a ; Matthias Trö ; ltzsch^b ; Jan Kü ; hnisch^d ; Michael Ehrenfeld^b ; Sven Otto^b
• 关键词：Osteomyelitis ; MSCs ; pH ; Proliferation ; Osteogenic differentiation ; Mineralization
• 刊名：Journal of Cranio-Maxillofacial Surgery
• 出版年：2016
• 出版时间：June 2016
• 年：2016
• 卷：44
• 期：6
• 页码：715-724
• 全文大小：3307 K

文摘

Osteomyelitis is a serious complication in oral and maxillofacial surgery affecting bone healing. Bone remodeling is not only controlled by cellular components but also by ionic and molecular composition of the extracellular fluids in which calcium phosphate salts are precipitated in a pH dependent manner.

Objective

To determine the effect of pH on self-renewal, osteogenic differentiation and matrix mineralization of mesenchymal stem cells (MSCs).

Methods

We selected three different pH values; acidic (6.3, 6.7), physiological (7.0–8.0) and severe alkaline (8.5). MSCs were cultured at different pH ranges, cell viability measured by WST-1, apoptosis detected by JC-1, senescence was analyzed by β-galactosidase whereas mineralization was detected by Alizarin Red and osteogenic differentiation analyzed by Real-time PCR.

Results

Self-renewal was affected by pH as well as matrix mineralization in which pH other than physiologic inhibited the deposition of extracellular matrix but did not affect MSCs differentiation as osteoblast markers were upregulated. The expression of osteocalcin and alkaline phosphatase activity was upregulated whereas osteopontin was downregulated under acidic pH.

Conclusion

pH affected MSCs self-renewal and mineralization without influencing osteogenic differentiation. Thus, future therapies, based on shifting acid-base balance toward the alkaline direction might be beneficial for prevention or treatment of osteomyelitis.