State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China.
Dept. of Implant, Stomatological Hospital, Southern Medical University, Guangzhou, Guangdong, China.
J Periodontol. 2020 Sep;91(9):1203-1212. doi: 10.1002/JPER.19-0247. Epub 2020 Feb 14.
Growth differentiation factor 11 (GDF11), a secreted member of the transforming growth factor-β superfamily, has recently been suggested as an anti-aging factor that declines with age in the bloodstream, and restoration of the youthful level by administration of its recombinant protein could reverse age-related dysfunctions. However, its effects on titanium implant osseointegration and mandibular bone during aging remain unknown.
Two-month-old and 18-month-old C57BL male mice were given daily intraperitoneal injections of recombinant GDF11 (rGDF11) or vehicle for 6 weeks. Experimental titanium implants were inserted into femurs on the fourth week. Inhibition of GDF11 function was achieved by GDF11 antibody. Implant-bearing femurs were subjected to histomorphometric analysis and biomechanical evaluation. Mandibles were scanned with micro-CT and decalcified for histological measurements.
In both young adult and aged mice, supraphysiologic GDF11 leads to a significantly decreased bone-to-implant contact ratio (BIC) and peri-implant bone volume/total volume (BV/TV) at the histologic level and reduced resistance at the biomechanical level, indicating weakened implant fixation. Moreover, rGDF11 administration resulted in less trabecular bone volume and thinner cortical thickness in the mandible, which was further compromised in the old animals. In contrast, inhibition of GDF11 improved peri-implant bone healing in old mice.
Rather than functioning as a rejuvenating factor, exogenous GDF11 negatively affects not only titanium implant healing but also mandibular bone in both young and old mice. In contrast, neutralization of endogenous GDF11 has positive effects on implant fixation in aged mice.
生长分化因子 11（GDF11）是转化生长因子-β超家族的一种分泌成员，最近被认为是一种抗衰老因子，其在血液中的水平随年龄的增长而下降，通过给予其重组蛋白可以恢复年轻水平，从而逆转与年龄相关的功能障碍。然而，其对衰老过程中钛植入物骨整合和下颌骨的影响尚不清楚。
将 2 个月大和 18 个月大的 C57BL 雄性小鼠分别给予重组 GDF11（rGDF11）或载体的每日腹腔内注射 6 周。第 4 周时将实验用钛植入物插入股骨。通过 GDF11 抗体抑制 GDF11 功能。对带植入物的股骨进行组织形态计量学分析和生物力学评估。使用 micro-CT 对下颌骨进行扫描，并进行脱钙后的组织学测量。
在年轻成年和老年小鼠中，超生理 GDF11 导致组织学水平上骨与植入物的接触比（BIC）和植入物周围骨体积/总体积（BV/TV）显著降低，生物力学水平上阻力降低，表明植入物固定减弱。此外，rGDF11 给药导致下颌骨的小梁骨体积减少和皮质厚度变薄，在老年动物中进一步受损。相比之下，抑制 GDF11 改善了老年小鼠的植入物周围骨愈合。
外源性 GDF11 不仅对钛植入物愈合，而且对年轻和老年小鼠的下颌骨都有负面影响，而不是作为一种 rejuvenating 因子。相反，内源性 GDF11 的中和对老年小鼠的植入物固定有积极影响。
