Older adults suffer more bone fractures with higher rates of healing complications and increased risk of morbidity and mortality. An improved understanding of the cellular and molecular mechanism of fracture healing and how such processes are perturbed with increasing age may allow for better treatment options to manage fractures in older adults. Macrophages are attractive therapeutics due to their role in several phases of fracture healing. After injury, bone marrow–derived macrophages are recruited to the injury and propagate the inflammatory response, contribute to resolution of inflammation, and promote bone regeneration. A tissue resident population of macrophages named osteal macrophages are present in the periosteum and are directly associated with osteoblasts and these cells contribute to bone formation. Here, we utilized bulk RNA sequencing to analyze the transcriptional activity of osteal macrophages from old and young mice present in primary calvarial cultures. Macrophages demonstrated a diverse transcriptional profile, expressing genes involved in immune function as well as wound healing and regeneration. Periostin was significantly downregulated in macrophages from old mice compared to young. Periostin is an extracellular matrix protein with important functions that promote osteoblast activity during bone regeneration. An age-related decrease of periostin expression was verified in the fracture callus of old mice compared to young. Young periostin knockout mice demonstrated attenuated fracture healing outcomes that reflected what is observed in old mice. This study supports an important role of periostin in fracture healing, and therapeutically targeting the age-related decrease in periostin may improve healing outcomes in older populations.

中文翻译：

---

年龄相关的骨膜素表达下降可能与老年小鼠骨折愈合减弱有关

老年人骨折的几率更高，愈合并发症的发生率更高，发病率和死亡率的风险也更高。更好地了解骨折愈合的细胞和分子机制以及这些过程如何随着年龄的增长而受到干扰，可能会为治疗老年人骨折提供更好的治疗选择。巨噬细胞由于其在骨折愈合的多个阶段中的作用而成为有吸引力的治疗方法。损伤后，骨髓来源的巨噬细胞被募集到损伤处并传播炎症反应，有助于炎症的消退并促进骨再生。称为骨巨噬细胞的组织驻留巨噬细胞群存在于骨膜中，与成骨细胞直接相关，这些细胞有助于骨形成。在这里，我们利用批量 RNA 测序来分析原代颅骨培养物中年老和年轻小鼠的骨巨噬细胞的转录活性。巨噬细胞表现出多样化的转录谱，表达参与免疫功能以及伤口愈合和再生的基因。与年轻小鼠相比，老年小鼠巨噬细胞中的骨膜素显着下调。骨膜素是一种细胞外基质蛋白，具有促进骨再生过程中成骨细胞活性的重要功能。与年轻小鼠相比，老年小鼠骨折愈伤组织中骨膜蛋白表达与年龄相关的下降得到证实。年轻的骨膜蛋白敲除小鼠表现出骨折愈合结果减弱，这反映了在年老小鼠中观察到的情况。这项研究支持骨膜素在骨折愈合中的重要作用，并且针对与年龄相关的骨膜素减少进行治疗可能会改善老年人群的愈合结果。