Mesenchymal progenitor cell markers in human articular cartilage: normal distribution and changes in osteoarthritis

Shawn P Grogan,Shigeru Miyaki,Martin K Lotz,Darryl D D'Lima,Hiroshi Asahara

doi:10.1186/ar2719

Shawn P Grogan, Shigeru Miyaki + Show 3 more

Open Access

https://doi.org/10.1186/ar2719

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Abstract

IntroductionRecent findings suggest that articular cartilage contains mesenchymal progenitor cells. The aim of this study was to examine the distribution of stem cell markers (Notch-1, Stro-1 and VCAM-1) and of molecules that modulate progenitor differentiation (Notch-1 and Sox9) in normal adult human articular cartilage and in osteoarthritis (OA) cartilage.MethodsExpression of the markers was analyzed by immunohistochemistry (IHC) and flow cytometry. Hoechst 33342 dye was used to identify and sort the cartilage side population (SP). Multilineage differentiation assays including chondrogenesis, osteogenesis and adipogenesis were performed on SP and non-SP (NSP) cells.ResultsA surprisingly high number (>45%) of cells were positive for Notch-1, Stro-1 and VCAM-1 throughout normal cartilage. Expression of these markers was higher in the superficial zone (SZ) of normal cartilage as compared to the middle zone (MZ) and deep zone (DZ). Non-fibrillated OA cartilage SZ showed reduced Notch-1 and Sox9 staining frequency, while Notch-1, Stro-1 and VCAM-1 positive cells were increased in the MZ. Most cells in OA clusters were positive for each molecule tested. The frequency of SP cells in cartilage was 0.14 ± 0.05% and no difference was found between normal and OA. SP cells displayed chondrogenic and osteogenic but not adipogenic differentiation potential.ConclusionsThese results show a surprisingly high number of cells that express putative progenitor cell markers in human cartilage. In contrast, the percentage of SP cells is much lower and within the range of expected stem cell frequency. Thus, markers such as Notch-1, Stro-1 or VCAM-1 may not be useful to identify progenitors in cartilage. Instead, their increased expression in OA cartilage implicates involvement in the abnormal cell activation and differentiation process characteristic of OA.

Highlights

Recent findings suggest that articular cartilage contains mesenchymal progenitor cells
A surprisingly high number (>45%) of cells were positive for Notch-1, Stro-1 and vascular cell adhesion molecule (VCAM)-1 throughout normal cartilage
Expression of these markers was higher in the superficial zone (SZ) of normal cartilage as compared to the middle zone (MZ) and deep zone (DZ)

Summary

Introduction

Recent findings suggest that articular cartilage contains mesenchymal progenitor cells. The limited repair capacity of adult articular cartilage represents one factor involved in the development of progressive cartilage degeneration and osteoarthritis (OA) following cartilage injury This notion was previously related to the absence of an inflammatory response, the putative absence and lack of access to stem cells in cartilage [1,2], and intrinsic limitations of adult human articular chondrocytes (AHAC) to repair tissue damage [3]. Cells in OA cartilage are activated as evidenced by the increased expression of a large number of genes and certain cells proliferate to form the characteristic cell clusters [6,7] This cell activation is associated with abnormal cell differentiation and represents a central pathogenetic mechanism in OA [6,7,8,9]. A new interpretation of the cellular responses in OA tissue is the possible involvement of resident cartilage progenitor cells [13] and is consistent with our previous report of increased progenitor marker expression in OA cartilage [14]

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