Next Article in Journal
Changes in DNA Methylation from Age 18 to Pregnancy in Type 1, 2, and 17 T Helper and Regulatory T-Cells Pathway Genes
Next Article in Special Issue
Genetic Determinants of Antibody Levels in Cerebrospinal Fluid in Multiple Sclerosis: Possible Links to Endogenous Retroviruses
Previous Article in Journal
Role of Zinc Homeostasis in the Pathogenesis of Diabetes and Obesity
Previous Article in Special Issue
Do Neuroendocrine Peptides and Their Receptors Qualify as Novel Therapeutic Targets in Osteoarthritis?
Article Menu
Issue 2 (February) cover image

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2018, 19(2), 475; https://doi.org/10.3390/ijms19020475

Alterations of Subchondral Bone Progenitor Cells in Human Knee and Hip Osteoarthritis Lead to a Bone Sclerosis Phenotype

1
Orthopaedic Department, University Hospital of Basel, 4031 Basel, Switzerland
2
Tissue Engineering, Department of Biomedicine, University Hospital of Basel, 4031 Basel, Switzerland
3
Department of Traumatology, University Hospital Centre Sestre Milosrdnice, 10000 Zagreb, Croatia
4
Department of Spine Surgery, University Hospital of Basel, 4031 Basel, Switzerland
5
Department of Rheumatology, University Hospital Lausanne (CHUV), 1005 Lausanne, Switzerland
6
Department of Biomedical Engineering, University Hospital of Basel, 4123 Allschwil, Switzerland
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 26 December 2017 / Revised: 23 January 2018 / Accepted: 26 January 2018 / Published: 6 February 2018
(This article belongs to the Special Issue Musculoskeletal Diseases Therapy)
View Full-Text   |   Download PDF [18703 KB, uploaded 6 February 2018]   |  

Abstract

Subchondral bone tissue plays a key role in the initiation and progression of human and experimental osteoarthritis and has received considerable interest as a treatment target. Elevated bone turnover and remodeling leads to subchondral bone sclerosis that is characterized by an increase in bone material that is less mineralized. The aim of this study was to investigate whether perturbations in subchondral bone-resident progenitor cells might play a role in aberrant bone formation in osteoarthritis. Colony formation assays indicated similar clonogenicity of progenitor cells from non-sclerotic and sclerotic subchondral trabecular bone tissues of osteoarthritic knee and hip joints compared with controls from iliac crest bone. However, the osteogenic potential at the clonal level was approximately two-fold higher in osteoarthritis than controls. An osteogenic differentiation assay indicated an efficient induction of alkaline phosphatase activity but blunted in vitro matrix mineralization irrespective of the presence of sclerosis. Micro-computed tomography and histology demonstrated the formation of de novo calcified tissues by osteoblast-like cells in an ectopic implantation model. The expression of bone sialoprotein, a marker for osteoblast maturation and mineralization, was significantly less in sclerotic progenitor cells. Perturbation of resident progenitor cell function is associated with subchondral bone sclerosis and may be a treatment target for osteoarthritis. View Full-Text
Keywords: osteoarthritis; subchondral bone; osteoprogenitors; osteogenic differentiation; ectopic bone formation; clonogenicity; computed tomography osteoarthritis; subchondral bone; osteoprogenitors; osteogenic differentiation; ectopic bone formation; clonogenicity; computed tomography
Figures

Graphical abstract

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Share & Cite This Article

MDPI and ACS Style

Bianco, D.; Todorov, A.; Čengić, T.; Pagenstert, G.; Schären, S.; Netzer, C.; Hügle, T.; Geurts, J. Alterations of Subchondral Bone Progenitor Cells in Human Knee and Hip Osteoarthritis Lead to a Bone Sclerosis Phenotype. Int. J. Mol. Sci. 2018, 19, 475.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top