Age-related jawbone loss directly impact the function of oral cavity resulted from tooth loss, implant failure, and jaw fracture. Numerous evidences show that age-related senescence of bone marrow stromal cells (BMSCs) play a critical role in bone loss, but little attention has been paid to jawbone. Here, we delineated the critical role of sirtuin family protein 6 (SIRT6) in senescence, autophagy, and osteogenesis of BMSCs from jawbones. Radiography analysis showed less jawbone quality in elderly than young people. We also showed that SIRT6 expression decreased in bone tissue and BMSCs from the elderly by immunochemical staining. BMSCs from the elderly exhibited decreased osteogenic differentiation and inclined senescence which these phenotypes could be simulated by SIRT6 knockdown. Furthermore, accompanied with the inhibition of SIRT6, the autophagy level and ostogenesis of BMSCs was also decreased. However, using rapamycin, an autophagy activator, could rescue these adverse effects of BMSCs caused by SIRT6 inhibition. Mechanistically, SIRT6 regulated the autophagy and osteogenesis of BMSCs by activating AKT-mTOR pathway, at least in part. Finally, a decreased jawbone quality was shown in SIRT6 haploinsufficiency mice by Wnt1 specific tissue knockdown (Wnt1-Cre;SIRT6^fl/+) model. Taken together, our data revealed that SIRT6 adjusted senescence and osteogenesis of BMSCs via altering autophagy level, and associated with age-related bone loss. SIRT6 could be as a promising therapeutic target for age-related osteoporosis of jawbone.

中文翻译：

---

通过调节骨髓基质细胞的衰老和自噬，SIRT6在颚骨中的年龄依赖性作用。

与年龄有关的颚骨丢失直接影响到因牙齿脱落，植入物衰竭和颌骨骨折而导致的口腔功能。大量证据表明，与年龄相关的骨髓基质细胞（BMSC）衰老在骨质流失中起关键作用，但对颌骨的关注却很少。在这里，我们描述了瑟土因家族蛋白6（SIRT6）在下颌骨BMSCs的衰老，自噬和成骨中的关键作用。射线照相分析显示，老年人的颚骨质量比年轻人少。我们还显示，通过免疫化学染色，老年人的骨组织和BMSC中SIRT6表达降低。老年人的骨髓间充质干细胞表现出减少的成骨分化和倾斜衰老，这些表型可以通过SIRT6敲低来模拟。此外，伴随着SIRT6的抑制，BMSCs的自噬水平和成骨率也降低。但是，使用雷帕霉素（一种自噬激活剂）可以挽救由SIRT6抑制引起的BMSC的这些不良反应。从机制上讲，SIRT6至少部分地通过激活AKT-mTOR途径来调节BMSC的自噬和成骨作用。最后，通过Wnt1特异性组织敲除，SIRT6单倍剂量不足小鼠的颚骨质量降低（Wnt1-Cre; SIRT6 ^{fl / +}）模型。两者合计，我们的数据表明，SIRT6通过改变自噬水平来调节BMSC的衰老和成骨，并与年龄相关的骨质流失相关。SIRT6可以作为与年龄相关的颚骨骨质疏松症的有希望的治疗靶标。