Muluke M, Gold T, Kiefhaber K, Al-Sahli A, Celenti R, Jiang H, Cremers S, Van Dyke T, Schulze-Späte U
Division of Periodontics, Columbia University College of Dental Medicine, New York, NY, USA Institute of Human Nutrition, Columbia University, New York, NY, USA.
Division of Periodontics, Columbia University College of Dental Medicine, New York, NY, USA.
J Dent Res. 2016 Feb;95(2):223-9. doi: 10.1177/0022034515609882. Epub 2015 Oct 8.
Obesity is associated with abnormal lipid metabolism and impaired bone homeostasis. The aim of our study was to investigate the impact of specific elevated fatty acid (FA) levels on alveolar bone loss in a Porphyromonas gingivalis-induced model of periodontal disease and to analyze underlying cellular mechanisms in bone-resorbing osteoclasts and bone-forming osteoblasts in mice. Four-week-old male C57BL/6 mice were randomly divided in groups and subjected to a palmitic acid (PA)- or oleic acid (OA)-enriched high-fat diet (HFD) (20% of calories from FA) or a normal caloric diet (C group) (10% of calories from FA) for 16 wk. Starting at week 10, mice were infected orally with P. gingivalis (W50) or placebo to induce alveolar bone loss. Animals were sacrificed, and percentage fat, serum inflammation (tumor necrosis factor [TNF]-α), and bone metabolism (osteocalcin [OC], carboxy-terminal collagen crosslinks [CTX], and N-terminal propeptides of type I procollagen [P1NP]) markers were measured. Osteoblasts and osteoclasts were cultured in the presence of elevated PA or OA levels and exposed to P. gingivalis. Animals on FA-enriched diets weighed significantly more compared with animals on a normal caloric diet (P < 0.05). Both obese groups had similar percentages of fat (P = nonsignificant); however, alveolar bone loss was significantly greater in animals that were on the PA-enriched HFD (P < 0.05). TNF-α levels were highest in the PA group (P < 0.001) and increased in all groups in response to P. gingivalis inoculation (P < 0.01), whereas bone remodeling markers OC, CTX, and P1NP were lowest in the PA group (P < 0.001) and highest in the C group. Bacterial challenge decreased bone metabolism markers in all groups (P < 0.01). Further, osteoclasts showed an augmented inflammatory response to P. gingivalis in the presence of hyperlipidemic PA levels as opposed to OA cultures, which responded similarly to controls. These findings indicate that the specific FA profile of diet rather than weight gain and obesity alone modulates bone metabolism and can therefore influence alveolar bone loss.
肥胖与脂质代谢异常及骨稳态受损有关。我们研究的目的是在牙龈卟啉单胞菌诱导的牙周病模型中,研究特定升高的脂肪酸(FA)水平对牙槽骨丢失的影响,并分析小鼠破骨细胞和成骨细胞中潜在的细胞机制。将4周龄雄性C57BL/6小鼠随机分组,给予富含棕榈酸(PA)或油酸(OA)的高脂饮食(HFD)(FA提供20%的热量)或正常热量饮食(C组)(FA提供10%的热量),持续16周。从第10周开始,小鼠经口感染牙龈卟啉单胞菌(W50)或给予安慰剂以诱导牙槽骨丢失。处死动物,测量脂肪百分比、血清炎症指标(肿瘤坏死因子[TNF]-α)和骨代谢指标(骨钙素[OC]、I型前胶原羧基末端交联肽[CTX]和I型前胶原N端前肽[P1NP])。在PA或OA水平升高的情况下培养成骨细胞和破骨细胞,并使其暴露于牙龈卟啉单胞菌。与正常热量饮食的动物相比,富含FA饮食的动物体重显著增加(P<0.05)。两个肥胖组的脂肪百分比相似(P=无显著性差异);然而,富含PA的HFD组动物的牙槽骨丢失明显更大(P<0.05)。PA组的TNF-α水平最高(P<0.001),并且在所有组中,接种牙龈卟啉单胞菌后TNF-α水平均升高(P<0.01),而骨重塑指标OC、CTX和P1NP在PA组中最低(P<0.001),在C组中最高。细菌攻击使所有组的骨代谢指标降低(P<0.01)。此外,与OA培养物相比,在高脂血症PA水平存在的情况下,破骨细胞对牙龈卟啉单胞菌的炎症反应增强,而OA培养物的反应与对照组相似。这些发现表明,饮食中特定的FA谱而非单纯的体重增加和肥胖会调节骨代谢,因此会影响牙槽骨丢失。