Impact Factor 6.429

The 5th most cited journal in Immunology

Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2018.00417

The long pentraxin PTX3 plays a role in bone turnover and repair

  • 1Department of Physiology and Immunology, School of Medicine, University of Zagreb, Croatia
  • 2Croatian Institute for Brain research, School of Medicine, University of Zagreb, Croatia
  • 3Humanitas Clinical and Research Center, Italy
  • 4Department of Medical Biotechnologies and Translational Medicine, Università degli Studi di Milano, Italy
  • 5Department of Anatomy, School of Medicine, University of Zagreb, Croatia
  • 6Department of Reconstructive Sciences, University of Connecticut Health Center, United States
  • 7Humanitas University, Italy
  • 8The William Harvey Research Institute, Queen Mary University of London, United Kingdom

PTX3 is an inflammatory mediator acting as a fluid phase pattern recognition molecule and playing an essential role in innate immunity and matrix remodeling. Inflammatory mediators also contribute to skeletal homeostasis, operating at multiple levels in physiological and pathological conditions. The present study was designed to investigate the role of PTX3 in physiological skeletal remodeling and bone healing. Micro-computed tomography (CT) and bone histomorphometry of distal femur showed that PTX3 gene-targeted female and male mice (ptx3-/-) had lower trabecular bone volume than their wild-type (ptx3+/+) littermates (BV/TV by CT: 3.50 ± 1.31 vs 6.09 ± 1.17 for females, p<0.0001; BV/TV 9.06 ± 1.89 vs 10.47 ± 1.97 for males, p=0.0435). In addition, CT revealed lower trabecular bone volume in second lumbar vertebra of ptx3-/- mice. PTX3 was increasingly expressed during osteoblast maturation in vitro, and was able to reverse the negative effect of fibroblast growth factor 2 (FGF2) on osteoblast differentiation. This effect was specific for the N-terminal domain of PTX3 that contains the FGF2 binding site. By using the closed transversal tibial fracture model we found that ptx3-/- female mice formed significantly less mineralized callus during the anabolic phase following fracture injury compared to ptx3+/+ mice (BV/TV 15.33 ± 2.32 vs 19.66 ± 4.32, p=0.0195). Non-hematopoietic periosteal cells highly up-regulated PTX3 expression during the initial phase of fracture healing, particularly CD51+ and Sma+ osteoprogenitor subsets, and callus tissue exhibited concomitant expression of PTX3 and FGF2 around the fracture site. Thus, PTX3 supports maintenance of the bone mass possibly by inhibiting FGF2 and its negative impact on bone formation. Moreover, PTX3 enables timely occurring sequence of callus mineralization after bone fracture injury. These results indicate that PTX3 plays an important role in bone homeostasis and in proper matrix mineralization during fracture repair, a reflection of the function of this molecule in tissue homeostasis and repair.

Keywords: PTX3, FGF2, Inflammation, bone turnover, bone healing, Osteoblasts, Osteoclasts

Received: 20 Aug 2017; Accepted: 15 Feb 2018.

Edited by:

Fabrice Cognasse, Groupe Sur L'immunité Des Muqueuses Et Agents Pathogènes (GIMAP), France

Reviewed by:

Catarina R. Almeida, University of Aveiro, Portugal
Darrell Pilling, Texas A&M University College Station, United States
Eun-Ju Chang, University of Ulsan College of Medicine, South Korea  

Copyright: © 2018 Grčević, Sironi, Valentino, Deban, Cvija, Inforzato, Kovačić, Katavić, Kelava, Kalajzić, Mantovani and Bottazzi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Barbara Bottazzi, Humanitas Clinical and Research Center, Via Manzoni,113, Rozzano, 20089, Milan, Italy,