Cellular origin of neocartilage formed at wound edges of articular cartilage in a tissue culture experiment.
OBJECTIVE
The regeneration capacity of cartilage in general is limited. Complete repair of partial thickness articular cartilage has only been reported in a fetal sheep model. However, in long-term culture studies of articular cartilage explants we have observed outgrowth of chondrocytes and neocartilage formation at wound edges. This illustrates that under optimal circumstances articular cartilage is capable to regenerate hyaline cartilage. Recent studies suggest the presence of mesenchymal stem cells in articular cartilage. In the present study we investigated the origin of chondrocyte outgrowth and neocartilage formation at wound edges from immature and mature articular bovine cartilage explants in vitro, in order to understand which cells are responsible for repair.


METHODS
Full-thickness explants from immature and mature animals were cultured for 4 weeks and superficial and deep zone cartilage explants of immature animals were separately cultured.


RESULTS
Significant more outgrowth was observed from immature explants as compared to mature explants. At wound edges of immature explants, this outgrowth showed high cell-densities, rounded cells, the extracellular matrix contained proteoglycans and collagen types I and II. We found proliferation activity both in the superficial zone and deep zone chondrocytes in immature explants, using the Ki67 proliferation marker. In the experiment culturing immature superficial and deep zone cartilage explants separately, there was abundant new tissue formation originating from deep cartilage and almost no outgrowth from the superficial cartilage. This indicates that neocartilage originates from chondrocytes in the deep zone cartilage and not from chondrocytes in the superficial zone cartilage.


CONCLUSIONS
Present data can help to understand wound healing in partial-thickness and full-thickness defects of immature and mature cartilage and can be of help in finding methods to stimulate the regeneration of articular cartilage.
Bos
P K
PK
Department of Orthopaedics, Erasmus MC, Rotterdam, The Netherlands. p.k.bos@erasmusmc.nl
Kops
N
N
Verhaar
J A N
JA
van Osch
G J V M
GJ
D000818:Animals; D002358:Cartilage, Articular / Q000166:cytology* / Q000378:metabolism; D002417:Cattle; D049109:Cell Proliferation; D019902:Chondrocytes / Q000166:cytology* / Q000276:immunology; D005109:Extracellular Matrix / Q000378:metabolism*; D024022:Fibrillar Collagens / Q000378:metabolism; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000276:immunology; D011509:Proteoglycans / Q000378:metabolism; D014945:Wound Healing / Q000502:physiology*
D024022:Fibrillar Collagens; D019394:Ki-67 Antigen; D011509:Proteoglycans