The surface of articular cartilage contains a progenitor cell population

Abstract

It is becoming increasingly apparent that articular cartilage growth is achieved by apposition from the articular surface. For such a mechanism to occur, a population of stem/progenitor cells must reside within the articular cartilage to provide transit amplifying progeny for growth. Here, we report on the isolation of an articular cartilage progenitor cell from the surface zone of articular cartilage using differential adhesion to fibronectin. This population of cells exhibits high affinity for fibronectin, possesses a high colony-forming efficiency and expresses the cell fate selector gene Notch 1. Inhibition of Notch signalling abolishes colony forming ability whilst activated Notch rescues this inhibition. The progenitor population also exhibits phenotypic plasticity in its differentiation pathway in an embryonic chick tracking system, such that chondroprogenitors can engraft into a variety of connective tissue types including bone, tendon and perimysium. The identification of a chondrocyte subpopulation with progenitor-like characteristics will allow for advances in our understanding of both cartilage growth and maintenance as well as provide novel solutions to articular cartilage repair.

Differences in matrix accumulation and hypertrophy in superficial and deep zone chondrocytes are controlled by bone morphogenetic protein

“…Previous studies including our own have reported several differences between SZC and DZC Darling and Athanasiou, 2005a;Darling and Athanasiou, 2005b;Darling et al, 2004;Dowthwaite et al, 2004;Eleswarapu et al, 2006;Marles et al, 1991;Siczkowski and Watt, 1990;Stephens et al, 1992;Waldman et al, 2003;Zanetti et al, 1985). In the current study, we have identified BMP as an important factor in the differential capacities of SZC and DZC to accumulate matrix and to hypertrophy.…”

“…In SZC, BMP overexpression did not cause cell enlargement or Runx2 upregulation, even while inducing the accumulation of a similar quality and quantity of PG-rich matrix as DZC. Previous studies have reported on the presence of stem like cells within neonatal bovine SZC (Dowthwaite et al, 2004). One possibility is that BMP increased PG accumulation in less mature cells without inducing hypertrophy.…”

Restricted differentiation potential of progenitor cell populations obtained from the equine superficial digital flexor tendon (SDFT)

“…We then considered that low density plating may not be a suitable method to isolate equine TSPCs and used differential adhesion to fibronectin as a stem cell isolation method, as previously described for epidermal stem cells and cartilage progenitor cells 24, 25. Plating onto substrates precoated with 1 μg/ml fibronectin promoted osteogenic differentiation of TSPCs grown in osteogenic media as assessed by Alizarin Red staining (Fig.…”

“…We also found that expression of osteogenic and chondrogenic marker genes was not entirely consistent with histological staining techniques for assessing differentiation. Fibronectin has been identified as a suitable substrate to maintain long term self renewal of embryonic stem cells and has been used for isolation of epidermal stem cells and cartilage progenitors 24, 25, 27. Fibronectin was therefore a good candidate ECM substrate for differential isolation of tendon stem cells.…”

Attributes of adult stem cells

“…Articular cartilage is a unique avascular load-bearing live tissue that does not normally self-repair. In the bovine, Dowthwaite et al [88] have suggested that stem/progenitor cells on the articular surfaces achieve appositional cartilage growth; these cells expressed the α5β1 integrin, the classical fibronectin receptor and Notch 1, which appeared to identify the most clonogenic cells. Osteoblastic progenitors can be recognized in vitro as cells that make colonies that express alkaline phosphatase (CFU-APs), and in humans there are on average ∼55 CFU-APs/10 6 nucleated bone marrow cells [89]; in both sexes there is a decline in frequency with age.…”