A new anabolic compound, LLP2A-Ale, reserves periodontal bone loss in mice through augmentation of bone formation
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(2020) 21:76
RESEARCH ARTICLE
Open Access
A new anabolic compound, LLP2A-Ale, reserves periodontal bone loss in mice through augmentation of bone formation Min Jiang1,2, Lixian Liu1,3, Ruiwu Liu4, Kit S. Lam4, Nancy E. Lane1 and Wei Yao1*
Abstract 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.
Background Periodontal disease (PD) is characterized by the progressive destruction of tooth-supporting alveolar bone and is mainly caused by chronic inflammation in response to persistent bacterial insult [1]. Currently, there are no effective medications that reverse PD-induced bone loss and regenerate new bone. There is an unmet medical need for nonsurgical therapeutic options to treat bone loss induced by PD. There are limited drug interventions for PD-induced alveolar bone loss that have been focused on reducing bone resorption. The most commonly available antiresorptive agents are bisphosphonates, * Correspondence: [email protected] 1 Department of Internal Medicine, University of California, Davis Medical Center, 4625 2nd Avenue, Sacramento, CA 95817, USA Full list of author information is available at the end of the article
which may be associated with an increased risk for osteonecrosis [2–4]. Other medications include antibiotics, and gluconate mouthwash, which reduce bacteria in the mouth but do not have direct effects on bone. To this end, we have developed a novel compound, LLP2AAle, that has an affinity for both bone (hydroxyapatite tissue) and mesenchymal stromal cells (MSCs). LLP2AAle improves the bone homing of both endogenous and exogenous MSCs [5, 6]. Several studies have been conducted to test this approach in animal models of primary osteoporosis, aging, glucocorticoid-induced bone fragility, and fracture healing [5, 7, 8].
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