gms | German Medical Science

Objectives: Pannexin 3 (Panx3) represents a member of the pannexin gap junction protein family, capable of promoting osteogenesis. It has been demonstrated that Panx3 is specifically expressed in bone-forming osteoblasts, with high expression levels in long bones and the axial skeleton. Previous studies showed that Panx3 is a target for the key osteoblast transcription factor Runx2, promotes osteoblast differentiation, and is required for normal bone development. Moreover, Panx3 was shown to be of crucial importance in skin wound healing through regulating inflammation and collagen remodeling.

Methods: Female WT and Panx3-deficient (Panx3^-/-) mice received a femoral osteotomy stabilized by an external fixator (Fx). Radiological and histological analyses of callus architecture were carried out at the early (day 7), intermediate (day 14), and late stages (day 21) of bone regeneration using µCT and non-decalcified cryo-sections, respectively. Expression of Panx3 was measured in the fracture callus as well as the intact femoral midshaft using qRT-PCR.

Results and conclusion: Compared to intact bone, expression of Panx3 in the fracture callus gradually increased throughout the course of bone regeneration. Panx3^-/- mice showed impaired bone regeneration 14 and 21 days after fracture compared to WT mice. µCT evaluation revealed a decrease in bone volume, tissue volume, and bone surface in the callus of Panx3^-/- mice. Histomorphometric evaluation of non-decalcified callus sections showed a reduced percentage of mineralized bone and an increased percentage of cartilage in the total callus area. Moreover, a high rate of fracture nonunion was observed in mutant animals. Taking together, our results suggest that Panx3 is crucially involved in the regulation of bone regeneration and may represent a promising therapeutic target to treat patients with impaired fracture healing.