Department of Immunology and Inflammation, Humanitas Clinical and Research Institute - IRCCS, Milan, Italy.
CNR-IRGB, Milan Unit, Milan, Italy.
Front Immunol. 2019 Nov 8;10:2628. doi: 10.3389/fimmu.2019.02628. eCollection 2019.
The innate immune system is equipped with a number of germ-line encoded soluble pattern recognition molecules (PRMs) that collectively mediate the humoral host response to infection and damage in cooperation with cells and tissues of the immune and non-immune compartments. Despite the impressive diversity in structure, source, and regulation across PRMs, these all share remarkably similar functions inasmuch as they recognize microbes and damaged tissues, activate complement, exert opsono-phagocytic activities, and regulate inflammation. The long pentraxin 3 (PTX3) is a prototypic soluble PRM. Long known as a major player in innate immunity, inflammation and matrix remodeling, only recently has PTX3 emerged as a mediator of bone homeostasis in rodents and humans. -targeted mice exhibit reduced trabecular volume during bone development, and impaired callus mineralization following experimental fracture. The murine gene is expressed by non-hematopoietic periosteal cells in the early phases of fracture healing, and by maturing osteoblasts. Human osteoblasts do express the PTX3 protein, whose levels positively correlate with bone density and osteoblast proliferation and maturation , thus pointing to a role in bone deposition. Contrasting evidence, however, suggest osteoclastogenesis-promoting effects of PTX3, where its expression has been associated with periodontitis, arthritis, and bone metastasis, conditions hallmarked by inflammation and bone resorption. Here, we review past and recent literature on the functions exerted by this long pentraxin in bone biology, with major emphasis on physiological skeletal remodeling, fracture healing, and chronic diseases of the bone.
先天免疫系统配备了许多种胚系编码的可溶性模式识别分子（PRMs），这些分子与免疫和非免疫区的细胞和组织一起，共同介导宿主对感染和损伤的体液反应。尽管 PRMs 在结构、来源和调节方面存在显著的多样性，但它们都具有惊人相似的功能，因为它们可以识别微生物和受损组织、激活补体、发挥调理吞噬作用以及调节炎症。长五聚素 3（PTX3）是一种典型的可溶性 PRM。PTX3 长期以来一直被认为是先天免疫、炎症和基质重塑的主要参与者，直到最近才被认为是啮齿动物和人类骨稳态的介质。PTX3 基因敲除小鼠在骨发育过程中表现出小梁体积减少，实验性骨折后骨痂矿化受损。该基因在骨折愈合的早期阶段由非造血的骨膜细胞表达，在成熟的成骨细胞中表达。人类成骨细胞确实表达了 PTX3 蛋白，其水平与骨密度和成骨细胞增殖和成熟呈正相关，因此表明其在骨沉积中具有作用。然而，相反的证据表明 PTX3 具有促进破骨细胞生成的作用，其表达与牙周炎、关节炎和骨转移有关，这些疾病的特点是炎症和骨吸收。在这里，我们回顾了过去和最近关于这种长五聚素在骨生物学中发挥的功能的文献，主要强调生理骨骼重塑、骨折愈合和骨骼的慢性疾病。
