TY - JOUR
T1 - A new anabolic compound, LLP2A-Ale, reserves periodontal bone loss in mice through augmentation of bone formation
AU - Jiang, Min
AU - Liu, Lixian
AU - Liu, Ruiwu
AU - Lam, Kit S.
AU - Lane, Nancy E.
AU - Yao, Wei
N1 - Funding Information:
This report was partially supported by U24DE026914 (J. Lotz overall PI; W. Yao project PI, to purchase animals and study materials). Acknowledgments
PY - 2020/12
Y1 - 2020/12
N2 - Background: Currently, there are no effective medications to reverse periodontal disease (PD)-induced bone loss. The objective of this study was to test a new anabolic compound, LLP2A-Ale, or with the combination treatment of mesenchymal stromal cell (MSC), in the treatment of bone loss secondary to PD. Methods: PD was induced in mice by placing a ligature around the second right molar. At one week after disease induction, the mice were treated with placebo, LLP2A-Ale, MSCs, or combination of LLP2A-Ale + MSCs, and euthanized at week 4. Results: We found that PD induced alveolar bone loss that was associated with reduced bone formation. LLP2A-Ale alone or in combination with MSCs sustained alveolar bone formation and reversed alveolar bone loss. Additionally, PD alone caused systemic inflammation and increased the circulating levels of G-CSF, IP-10, MIP-1a, and MIP2, which were suppressed by LLP2A-Ale +/− MSCs. LLP2A-Ale +/− MSCs increased bone formation at the peripheral skeletal site (distal femur), which was otherwise suppressed by PD. Conclusion: Our findings indicated that LLP2A-Ale treatment rescued alveolar bone loss caused by PD, primarily by increasing bone formation. LLP2A-Ale also attenuated the circulating levels of a series of inflammatory cytokines and reversed the PD-induced suppression of systemic bone formation.
AB - Background: Currently, there are no effective medications to reverse periodontal disease (PD)-induced bone loss. The objective of this study was to test a new anabolic compound, LLP2A-Ale, or with the combination treatment of mesenchymal stromal cell (MSC), in the treatment of bone loss secondary to PD. Methods: PD was induced in mice by placing a ligature around the second right molar. At one week after disease induction, the mice were treated with placebo, LLP2A-Ale, MSCs, or combination of LLP2A-Ale + MSCs, and euthanized at week 4. Results: We found that PD induced alveolar bone loss that was associated with reduced bone formation. LLP2A-Ale alone or in combination with MSCs sustained alveolar bone formation and reversed alveolar bone loss. Additionally, PD alone caused systemic inflammation and increased the circulating levels of G-CSF, IP-10, MIP-1a, and MIP2, which were suppressed by LLP2A-Ale +/− MSCs. LLP2A-Ale +/− MSCs increased bone formation at the peripheral skeletal site (distal femur), which was otherwise suppressed by PD. Conclusion: Our findings indicated that LLP2A-Ale treatment rescued alveolar bone loss caused by PD, primarily by increasing bone formation. LLP2A-Ale also attenuated the circulating levels of a series of inflammatory cytokines and reversed the PD-induced suppression of systemic bone formation.
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U2 - 10.1186/s40360-020-00454-x
DO - 10.1186/s40360-020-00454-x
M3 - Article
C2 - 33187558
AN - SCOPUS:85095941704
VL - 21
JO - BMC pharmacology & toxicology
JF - BMC pharmacology & toxicology
SN - 2050-6511
IS - 1
M1 - 76
ER -