Loss of tissue attachment as a consequence of bacterial infection and inflammation represents the main therapeutic target for the treatment of periodontitis. Cementoblasts, the cells that produce the mineralised tissue, cementum, that is responsible for connecting the soft periodontal tissue to the tooth, are a key cell type for maintaining/restoring tissue attachment following disease. Here we identify two distinct stem cell populations that contribute to cementoblast differentiation at different times. During postnatal development, cementoblasts are formed from perivascular-derived cells expressing CD90 and perivascular-associated cells that express Axin2. During adult homeostasis, only Wnt-responsive Axin2+ cells form cementoblasts but following experimental induction of periodontal disease, CD90+ cells become the main source of cementoblasts. We thus show that different populations resident stem cells are mobilised at different times and during disease to generate precursors for cementoblast differentiation and thus provide an insight into the targeting cells resident cells for novel therapeutic approaches. The differentiation of these stem cells into cementoblasts is however inhibited by bacterial products such as Lipopolysaccharides (LPS), emphasising that regeneration of periodontal ligament (PDL) soft tissue and restoration of attachment will require a multi-pronged approach. © AlphaMed Press 2020 SIGNIFICANCE STATEMENT: In this manuscript, we identified two different stem cell populations that are able to differentiate to cementoblasts in the periodontium. At development stages, both Axin2+ and CD90+ cell populations can give rise to cementoblasts whereas in adult homeostasis, only Axin2+ cell population continue to form cementoblasts. However, the CD90+ cells that normally remain in a quiescent state in adults, can respond during periodontal disease and form cementoblasts, but this stem cell regenerative ability is inhibited by bacterial metabolites. These results have profound implications for the both the use of exogenous cells and mobilization of resident cells as therapies to restore tissue following periodontal disease.
Stem cell contributions to cementoblast differentiation in healthy periodontal ligament and periodontitis.