Impairment of PTX3 expression in osteoblasts: a key element for osteoporosis

Abstract

Pentraxin 3 (PTX3) is a multifunctional glycoprotein regulating inflammatory response, cell proliferation and migration and deposition and remodelling of the extracellular matrix by a variety of cells. In this study, we investigated the possible role of PTX3 in bone homeostasis. To this end, we compared the expression and function of PTX3 in human osteoblasts of osteoporotic, osteoarthritic patients and young subjects not affected by bone diseases. Immunohistochemical analysis performed on bone head biopsies showed a close association between bone health and the number of osteoblasts expressing PTX3. Noteworthy, the proportion of PTX3-positive osteoblasts resulted to be significantly lower in osteoporotic patients compared with both young patients and osteoarthritic patients of the same age. Ex vivo culture of osteoblasts isolated from the three groups of patients confirmed in vivo observation. Specifically, we observed rare runt-related transcription factor 2 (RUNX2) immunopositive osteoblasts expressing PTX3 in cell cultures derived from osteoporotic patients and western blotting analysis showed 80% reduction of PTX3 in the corresponding culture extracts compared with young and osteoarthritic patients. The treatment of human osteoblast primary cultures derived from young patients with anti-PTX3 antibody dramatically affected osteoblast behaviour. Indeed, they lost the morphological and molecular features typical of mature osteoblasts, acquiring fibroblast-like shape and highly decreasing nuclear factor kappa-B ligand (RANKL) and RUNX2 expression. Also, the inhibition of PTX3 negatively affected osteoblast proliferation and their ability to form cell clusters and microhydroxyapatite crystals. Altogether, these results suggest a central role of PTX3 in bone homeostasis showing its involvement in osteoblast proliferation, differentiation and function.

Calcifications in prostate cancer: An active phenomenon mediated by epithelial cells with osteoblast‐phenotype

“…It is involved in inflammatory response, cell proliferation, cell migration, deposition, and remodeling of the extracellular matrix. In line with recent studies, that demonstrated the involvement of PTX3 is involved in osteoblast proliferation, differentiation and function (Scimeca et al, ), our results showed an increase in PTX3‐positive cells in prostate lesions with calcifications. Noteworthy, we observed a correlation between the presence of PTX3‐positive cancer cell and the formation of calcifications made of HA.…”

Radiological, Histological and Chemical Analysis of Breast Microcalcifications: Diagnostic Value and Biological Significance

“…Recently, we described PTX3 as a new possible marker of poor differentiated breast carcinomas [27]. In addition, we found that high levels of PTX3 are associated with better bone quality in humans and its functional inhibition in vitro hinder mature osteoblasts in producing HA crystals [15,28]. In line with these evidences, here we found a significantly higher PTX3 signal in the environment of malignant lesions presenting microcalcifications with respect to malignant lesions without microcalcifications.…”

Can microcalcifications' characteristics predict the risk of breast cancer metastasis to bone?

“…PTX3, also known as TNF-inducible gene 14 protein, is a molecule involved in several process of innate immunity [17,18] . It is also demonstrated that PTX3 have a role in the extracellular matrix formation as well as bone formation [9] . In…”

“…Among them, deserve particular mention the bone morphogenetic proteins 2 (BMP-2) and pentraxin-3 (PTX3). BMP-2 is currently considered the most powerful osteoblast induction factor [8] , whereas it is recently demonstrated the ability of PTX3 to induce both osteoblast proliferation and activity [9,10] . In particular, studies of Scimeca et al [7] highlighted the essential role of PTX3 in bone metabolisms founding a correlation between the impairment of PTX3 expression and the inhibition of osteoblast activity.…”