The Long Pentraxin PTX3 in Bone Homeostasis and Pathology

Abstract

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. Ptx3-targeted mice exhibit reduced trabecular volume during bone development, and impaired callus mineralization following experimental fracture. The murine gene is expressed in vivo by non-hematopoietic periosteal cells in the early phases of fracture healing, and in vitro by maturing osteoblasts. Human osteoblasts do express the PTX3 protein, whose levels positively correlate with bone density in vivo and osteoblast proliferation and maturation in vitro, 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.

The long pentraxin PTX3: a novel serum marker to improve the prediction of osteoporosis and osteoarthritis bone-related phenotypes

“…Although the main roles of PTX3 discovered so far were in host protection, harmful effects have been observed under pathophysiological conditions suggesting its dual role, even as a negative modulator in a mouse model of intestinal ischaemia and reperfusion [8]. In the last few years, several studies focused on the involvement of PTX3 in bone-related pathophysiological processes, such as ectopic calcifications formation and alteration of bone metabolism in ageing-related diseases [9,[10][11][12]. Interestingly, ageing-related diseases are closely related to inflammatory processes, two conditions belonging to the world of "inflammaging".…”

“…In the pathological context, tumour necrosis factor-alpha (TNF-α) leads to increased PTX3 expression in bone tissue, which results in an enhanced release of receptor activator of nuclear factor kappa-B ligand TNF alpha (RANKL) from osteoblast's precursors, directing their differentiation towards the osteoclastogenic lineage [18]. Moreover, an accumulation of PTX3 seems to occur in the arthritic joint, suggesting its involvement in triggering a local inflammatory process and degeneration of bone tissue [12]. These results indicate that PTX3 can act as an inflammatory mediator in promoting bone loss in inflammatory bone-erosive diseases [18].…”

The Role of PTX3 in Mineralization Processes and Aging-Related Bone Diseases

“…Indeed, it has been seen to be involved in HA crystals formation and breast cancer cells differentiation into Breast Osteoblast Like Cells (BOLCs). Finally, recent investigations highlighted a possible role of PTX3 in osteoblast activity and bone matrix formation in both human and mouse tissues (11)(12)(13)(14). Noteworthy, in these studies the impairment of PTX3 expression was correlated to the occurrence of osteoporosis and more in general with a significant decrease of osteoblast differentiation.…”

Control of Complement Activation by the Long Pentraxin PTX3: Implications in Age-Related Macular Degeneration

“…One of the ligands of FH is the long pentraxin 3 (PTX3) (Deban et al, 2008), a multimeric glycoprotein with a distinctive quaternary structure (Bottazzi et al, 1997;Inforzato et al, 2008;Inforzato et al, 2010;Inforzato et al, 2012) that is produced by a number of somatic and immune cells, and plays key roles in innate immunity, tissue remodeling, and inflammation (Doni et al, 2019;Parente et al, 2019;Parente et al, 2020). Current evidence indicates that PTX3 is locally made by the RPE in the presence of pro-inflammatory cytokines (Woo et al, 2013), and in conditions of oxidative stress (Wang et al, 2016;Hwang et al, 2019).…”