The long Pentraxin 3 plays a role in bone turnover and repair

Scientific paper - Original scientific paper

• Author: Danka Grčević
• Author: Marina Sironi
• Author: Sonia Valentino
• Author: Livija Deban
• Author: Hrvoje Cvija
• Author: Antonio Inforzato
• Author: Nataša Kovačić
• Author: Vedran Katavić
• Author: Tomislav Kelava
• Author: Ivo Kalajzić
• Author: Alberto Mantovani
• Author: Barbara Bottazzi
• Author's institution: University of Zagreb; School of Medicine
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Basic Medical Sciences

Abstract (english)

Pentraxin 3 (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. This study was designed to investigate
the role of PTX3 in physiological skeletal remodeling and bone healing. Micro-computed
tomography (μCT) 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 μCT: 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, μCT
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 17.05 ± 4.59 vs 20.47 ± 3.32, p = 0.0195). Nonhematopoietic
periosteal cells highly upregulated PTX3 expression during the initial phase
of fracture healing, particularly CD51+ and αSma+ 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 (english): Animals; Bone Remodeling/genetics; C-Reactive Protein/genetics; C-Reactive Protein/metabolism; Cell Differentiation; Cells, Cultured; Disease Models, Animal; Female; Fibroblast Growth Factor 2/metabolism; Fractures, Bone/metabolism; Humans; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Osteoblasts/physiology; Serum Amyloid P-Component/genetics; Serum Amyloid P-Component/metabolism; Tibia/surgery; Wound Healing/genetics; X-Ray Microtomography
• Language: english
• Publication type: Scientific paper - Original scientific paper
• Publication status: Published
• Peer review: Peer review
• Publication version: Published version
• Journal title: Frontiers in Immunology
• Numbering: vol. 9, p. 417
• p-ISSN: 1664-3224
• DOI: https://doi.org/10.3389/fimmu.2018.00417
• URN:NBN: urn:nbn:hr:105:636402
• Publication: 2018-03-05
• Document URL: https://doi.org/10.3389/fimmu.2018.00417
• Type of resource: Text
• Access conditions: Open access
• Created on: 2024-03-28 10:08:57