Nazzal Murad K, Battina Hanisha L, Tewari Nikhil P, Mostardo Sarah L, Nagaraj Rohit U, Zhou Donghui, Awosanya Olatundun D, Majety Saveda K, Samson Sue, Blosser Rachel J, Dadwal Ushashi C, Mulcrone Patrick L, Kacena Melissa A
Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Richard L. Roudebush Veterans' Administration Medical Center, Indianapolis, IN 46202, USA.
Aging (Albany NY). 2024 Nov 22;16(21):13181-13200. doi: 10.18632/aging.206077.
With aging, the risk of fractures and compromised healing increases. Angiogenesis plays a significant role in bone healing and is impaired with aging. We have previously shown the impact of megakaryocytes (MKs) in regulating bone healing. Notably, MKs produce factors known to promote angiogenesis. We examined the effects of conditioned media (CM) generated from MKs derived from young (3-4-month-old) and aged (22-24-month-old), male and female C57BL/6J mice on bone marrow endothelial cell (BMEC) growth and function. Female MK CM, regardless of age, caused a >65% increase in BMEC proliferation and improved vessel formation by >115%. Likewise, young male MK CM increased vessel formation by 160%. Although aged male MK CM resulted in >150% increases in the formation of vascular nodes and meshes, 62% fewer vessels formed compared to young male MK CM treatment. Aged female MK CM improved migration by over 2500%. However, aged female and male MK CM caused less wound closure. MK CM treatments also significantly altered the expression of several genes including PDGFRβ, CXCR4, and CD36 relative to controls and between ages. Further testing of mechanisms responsible for age-associated differences may allow for novel strategies to improve MK-mediated angiogenesis and bone healing, particularly within the aging population.
随着年龄增长，骨折风险及愈合受损风险增加。血管生成在骨愈合中起重要作用，且会随着衰老而受损。我们之前已表明巨核细胞（MKs）在调节骨愈合中的作用。值得注意的是，巨核细胞产生已知可促进血管生成的因子。我们检测了来自年轻（3 - 4月龄）和老年（22 - 24月龄）雄性和雌性C57BL/6J小鼠的巨核细胞所产生的条件培养基（CM）对骨髓内皮细胞（BMEC）生长和功能的影响。无论年龄如何，雌性巨核细胞条件培养基均可使骨髓内皮细胞增殖增加>65%，并使血管形成改善>115%。同样，年轻雄性巨核细胞条件培养基可使血管形成增加160%。尽管老年雄性巨核细胞条件培养基使血管节点和网的形成增加>150%，但与年轻雄性巨核细胞条件培养基处理相比，形成的血管减少了62%。老年雌性巨核细胞条件培养基使迁移改善超过2500%。然而，老年雌性和雄性巨核细胞条件培养基导致伤口闭合减少。与对照相比以及在不同年龄组之间，巨核细胞条件培养基处理还显著改变了包括血小板衍生生长因子受体β（PDGFRβ）、CXC趋化因子受体4（CXCR4）和血小板膜糖蛋白CD36在内的几种基因的表达。对与年龄相关差异的机制进行进一步测试，可能会产生新的策略来改善巨核细胞介导的血管生成和骨愈合，尤其是在老年人群中。
