In extraction wounds, PTH rescued ALN/DEX-induced impaired healing evidenced by high bone fill and promotion of soft tissue coverage. PTH’s ability to promote healing of ONJ in osteoporotic patients has been reported in case studies [16], however, its mechanisms are unknown. Our study may provide a biological explanation. In the current study, the ALN/DEX treatment significantly suppressed osteoclasts in the extraction wounds. Osteoclast recovery, however, appeared to not be critical for healing since osteoclast surface was significantly suppressed in the healed LY3039478 solubility dmso wounds of the ALN/DEX-PTH group.

Rather, the VX-689 cell line reduction of empty osteocyte lacunae appeared to be associated with healing. PTH significantly reduced the empty lacunae in both the ALN/DEX- and VC-treated rats, suggesting that PTH may promote osteocyte survival in extraction wounds. The significant reduction in empty osteocyte lacunae was observed not only in the extraction wounds but also in the tibial defects. In the tibial defects, it is likely that the surgical drill created damage in the bone and induced osteocyte death. PTH significantly promoted osteocyte survival in both the ALN/DEX and VC-treated groups. Furthermore, PTH appeared to promote the survival of bone marrow cells as suggested by the numbers of TUNEL+ bone marrow cells that were significantly suppressed

by NVP-AUY922 datasheet PTH in the tibial defects. Intermittent PTH is known to have antiapoptotic effects in mature osteoblasts [41], but our findings suggest that PTH might have antiapoptotic effects on other cell types including osteocytes in osseous wounds. In this study, PTH suppressed PMN infiltration and promoted collagen apposition significantly in the extraction wounds. Although unclear, we speculate PAK6 that the suppression of osteocyte death by PTH reduced inflammatory responses and therefore suppressed PMN infiltration, and such a diminution

in inflammatory responses promoted soft tissue healing by increasing collagen apposition. Abtahi et al. compared the incidence of necrotic lesions with and without wound coverage post-extractions in rats on ALN/DEX and found that all extraction wounds developed necrotic lesions when the wounds were left open, but with the wound coverage, no necrotic lesions occurred [42]. In the present study, the tooth extraction wounds were left open, while the tibial defects were closed. Extraction wounds are typically left open in humans, so it is possible that if the oral wounds were closed in this study, they could have healed in a similar manner to the tibial wounds. The observed differences in this study could be, therefore, to a small extent attributed to the presence or absence of wound closure. Rats heal rapidly after tooth extraction; epithelial coverage occurs in approximately 8 days and bone fill happens in approximately 3 weeks [5].