Differential matrix degradation and turnover in early cartilage lesions of human knee and ankle joints.
OBJECTIVE
To determine whether there are differences in matrix turnover within early cartilage lesions of the ankle (talocrural) joint compared with the knee (tibiofemoral) joint that may help explain differences in the prevalence of osteoarthritis in these 2 joints.


METHODS
Cartilage removed from lesions of the tali and femoral condyles was analyzed for type IIB collagen messenger RNA, C-terminal type II procollagen propeptide (CPII), the collagenase cleavage neoepitope (Col2-3/4C(short)), and the denaturation epitope (Col2-3/4m). The content of collagen, glycosaminoglycan, and epitope 846 of aggrecan was quantitated.


RESULTS
In ankle lesions, there was an up-regulation of markers of synthesis (CPII [P = 0.07]; epitope 846 [P < or = 0.0001]), but these were down-regulated in the knee (CPII [P = 0.1]; epitope 846 [P = 0.004]). In lesions of the knee, but not the ankle, there was an up-regulation of collagen degradation markers (P = 0.008). On a molar basis, there was 24 times more cleavage epitope than denaturation epitope in knee lesions compared with ankle lesions.


CONCLUSIONS
The up-regulation of matrix turnover that is seen in early cartilage lesions of the ankle would appear to represent an attempt to repair the damaged matrix. The increase in collagen synthesis and aggrecan turnover seen in ankle lesions is absent from knee lesions. Instead, there is an increase in type II collagen cleavage. Together with the differences in collagen denaturation, these changes point to an emphasis on matrix assembly during early lesion development in the ankle and to degradation in the knee, resulting in fundamental differences in matrix turnover in these lesions.
Aurich
Matthias
M
Department of Biochemistry, Rush Medical College at Rush University Medical Center, 1653 West Congress Parkway, Chicago, IL 60612, USA.
Squires
Ginette R
GR
Reiner
Agnes
A
Mollenhauer
Juergen A
JA
Kuettner
Klaus E
KE
Poole
A Robin
AR
Cole
Ada A
AA
D000328:Adult; D053674:Aggrecans; D000843:Ankle Joint / Q000378:metabolism* / Q000473:pathology; D002358:Cartilage, Articular / Q000378:metabolism* / Q000473:pathology; D024043:Collagen Type II / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007719:Knee Joint / Q000378:metabolism* / Q000473:pathology; D037181:Lectins, C-Type; D008875:Middle Aged; D010003:Osteoarthritis / Q000378:metabolism* / Q000473:pathology; D011509:Proteoglycans / Q000378:metabolism; D013997:Time Factors
D053674:Aggrecans; D024043:Collagen Type II; D016326:Extracellular Matrix Proteins; D037181:Lectins, C-Type; D011509:Proteoglycans