T. Aigner et al., DIFFERENTIAL EXPRESSION OF COLLAGEN TYPE-I, TYPE-II, TYPE-III, AND TYPE-X IN HUMAN OSTEOPHYTES, Laboratory investigation, 73(2), 1995, pp. 236-243
BACKGROUND: Osteophytes are neoplastic cartilaginous and osseous protr
usions growing at the margins of osteoarthritic joints. Their formatio
n involves complex patterns of cellular proliferation, differentiation
, as well as matrix synthesis and turnover that are poorly understood.
EXPERIMENTAL DESIGN: Here we report on an experimental approach using
in situ hybridization and immunohistology to elucidate pathways of ch
ondrocyte differentiation in human osteophytes. Ab and cDNA probes for
collagen types were used as specific parameters for chondrocyte pheno
types. RESULTS: In early precartilaginous mesenchymal tissue, cytoplas
mic mRNA for alpha 1(I) and alpha 1(III) collagen genes (Col1A1 and Co
l3A1) were found by in situ hybridization, correlating with the distri
bution of type I and III collagen as revealed by Ab staining. Strong e
xpression of type II collagen both at mRNA and protein levels was the
hallmark of chondrogenic differentiation in the cartilaginous zone of
osteophytes. Type II collagen expression increased in all cartilaginou
s and fibrocartilaginous areas with growth and maturation of osteophyt
es. The signal intensity obtained after in situ hybridization with a C
OL2A1 probe was high and corresponded to that obtained in fetal cartil
age, whereas normal adult articular cartilage usually did not show mea
surable type II collagen expression. In fibrocartilaginous areas, the
most abundant, but heterogeneous tissue type seen in osteophytes, type
II and III collagen mRNA expression overlapped considerably. Type III
collagen was scattered, both pericellularly and interterritorially, o
ver the whole osteophyte, excluding bone and chondrocytic cells of the
deep zone. The strongest type I collagen expression was seen in bone
and in the superficial fibrous layer. In areas of endochondral ossific
ation, large chondrocytes were found expressing type X collagen, a spe
cific marker for hypertrophic chondrocytes. CONCLUSIONS: These results
show that discrete stages of cartilage differentiation can be precise
ly followed in osteophytes using collagen type-specific cDNA probes an
d Ab as markers. In addition, a fibrocartilaginous chondrocyte phenoty
pe was identified that expresses type II and III, but not type I colla
gen.