Future directions for designing periodontal regenerative therapies hinge on characterization of cells associated with periodontal tissues and on signals instrumental in regulating their behavior. Studies here focused on determining the responsiveness of putative cementoblast progenitor cells (follicle cells), periodontal ligament cells, and cementoblasts to specific factors. Cementoblasts (OCCM), periodontal ligament (SVPDL) cells, and follicle cells (SVF4) were isolated from mouse tissues and immortalized, where SV indicates the use of SV-40 for immortalization. Cultured cells were examined for response to parathyroid hormone-related protein (PTHrP), bone morphogenetic protein-2 (BMP-2), and enamel matrix derivative (EMD) using RT-PCR, Northern analysis, and in vitro and in vivo mineralization assays. Results showed that the three cell lines varied in their expression of bone sialoprotein (BSP) and osteocalcin (OCN), and in their capacity to promote mineralization. RT-PCR indicated that all cell lines had PTH/PTHrP-R1 and BMP receptors; however, the response of individual cell lines to PTHrP, BMP-2, and EMD was quite different. Such dissimilarities in responsiveness associated with cell type may need to be considered when designing regenerative therapies.