Pdlsc-Cm Targets Hapln1 To Reduce Root Resorption After Replantation

We aim to evaluate the therapeutic effect and potential target of periodontal ligament stem cell-conditioned medium (PDLSC-CM) to reduce root resorption in delayed replanted tooth. All experimental procedures have been approved by the Ethics Committee of Hebei Medical University. Histopathological staining was used to compare inflammatory and osteoclast-related factors expression in patients with delayed and non-replanted tooth. Micro-CT and histopathological staining were used to evaluate PDLSC-CM efficacy in delayed tooth replantation rat models. Proteomics was employed to screen potential target and AAV vector was constructed to validate. Human delayed replantation cases exhibited obvious root resorption accompanied by high expressions of inflammatory cytokines (TNF-α and IL-1β) and osteoclast-related factors (RANKL and MMP9) in periapical tissue. PDLSC-CM reduced root resorption and inhibited the expression of inflammatory cytokines (TNF-α and IL-1β) and osteoclast-related factors (RANKL and MMP9) in root and periapical tissue of delayed replantation of avulsed tooth in rats. PDLSC-CM downregulated the expression of hyaluronan and proteoglycan link protein-1 (HAPLN1) particularly in macrophages according by proteomics and molecular biology, thereby inhibits inflammation and osteoclastogenesis of delayed replanted tooth root. Overexpression of HAPLN1 abolished the effect of PDLSC-CM. Downregulation of HAPLN1 in macrophages is crucial for PDLSC-CM to mitigate root resorption by alleviating inflammatory response and inhibiting osteoclast generation in delayed replanted tooth. PDLSC-CM is a promising preservation medium for avulsed teeth, and the development of drug candidate targeting HAPLN1 has favorable clinical prospects.