Objectives When bone filling materials are applied onto the periodontal tissues in vivo, they interact with the injured periodontal ligament (PDL) tissue and modulate its activity. This may lead to mesenchymal stem cells (MSCs) recruitment from bone marrow and initiate bone regeneration. Our hypothesis is that the filling materials affect PDL cells and MSCs functional activities by modulating PDL C5a secretion and subsequent MSCs proliferation and recruitment. Materials and methods Materials' extracts were prepared from 3 bone-grafting materials: Gen-Os ® of equine and porcine origins and bovine Bio-Oss ®. Expression and secretion of C5a protein by injured PDL cells were investigated by RT-PCR and ELISA. MSCs proliferation was analyzed by MTT assay. C5a binding to MSCs C5aR and its phosphorylation was studied by ELISA. C5a implication in MSCs recruitment toward injured PDL cells was investigated using Boyden chambers. Results MSCs proliferation significantly increased with Gen-Os ® materials but significantly decreased with Bio-Oss ® .C5a secretion slightly increased with Bio-Oss ® while its level doubled with Gen-Os ® materials. C5a fixation on MSCs C5aR and its phosphorylation significantly increased with Gen-Os ® materials but not with Bio-Oss ®. MSCs recruitment toward injured PDL cells increased with the three materials but was significantly higher with Gen-Os ® materials than with Bio-Oss ® .Adding C5a antagonist inhibited MSCs recruitment demonstrating a C5a-mediated migration. Conclusions Injured PDL cells secrete C5a leading MSCs proliferation and recruitment to the PDL injured cells. Gen-Os ® materials enhanced both C5a secretion by injured PDL cells and MSCs recruitment. Bio-Oss ® inhibited MSCs and was less efficient than Gen-Os ® materials in inducing MSCs recruitment. Clinical relevance Within the limits of this study in vitro, Gen-Os ® filling materials have a higher potential than Bio-Oss ® on MSCs proliferation and C5a-dependent recruitment to the PDL injury site and the subsequent bone regeneration.