Linköping University Medical Dissertations No. 548

Maturation-Dependent Normal and Injury-Induced Changes
in Rabbit Knee Articular Cartilage

Akademisk avhandling
som för avläggande av medicine doktorsexamen kommer att offentligen försvaras i Berzeliussalen, plan 09, Hälsouniversitetet, Universitetssjukhuset, Linköping, torsdag 26 mars 1998, kl 09:00

av

Xiaochun Wei, MD

Fakultetsopponent
Docent Leif Ryd, Department of Orthopedics, University Hospital,
Lund University, Lund, Sweden

The thesis is based on the following studies

I.. Wei X, Gao J, Messner K. Concentrations of proteoglycan fragments in relation to maturation, sex, and time of day: Physiologic variations in knee joint fluid of rabbits. Acta Orthop Scand 1996;67:185-188.

II. Wei X, Räsänen T, Messner K. Maturation-related subchondral bone volume fraction and compressive properties of rabbit knee articular cartilage. Submitted

III. Wei X, Gao J, Messner K. Maturation-dependent repair of untreated osteochondral defects in the rabbit knee joint. J Biomed Mat Res 1997;34:63-72.

IV. Wei X, Messner K. Maturation-dependent durability of repair tissue in untreated osteochondral defects of the rabbit knee joint. Submitted.

V. Wei X, Messner K. Age- and injury-dependent concentrations of transforming growth factor- b1 and proteoglycan fragments in rabbit knee joint fluid. Osteoarthritis and Cartilage 1998;6:10-18.

ABSTRACT

Cartilage injuries are common in sports. and may on the long term develop to osteoarthritis. Prosthetic joint replacement is not satisfactory for young active individuals with extended cartilage injuries in large weight-bearing joints. In these cases, a treatment is needed which reestablishes normal joint surfaces by biologic means. Though different cartilage repair enhancing methods have been tried, up till now none of them has achieved regrowth of hyaline cartilage which duplicates the structure and functions of normal articular cartilage. More knowledge is needed to understand the response of articular cartilage to injury. Moreover, a better understanding of how articular cartilage develops may open ways to improve the repair response. The purpose of this work was to investigate maturation-related changes of articular cartilage during postnatal maturation, and to investigate the natural healing response to full-thickness cartilage injury as a function of maturation stage.

Physiologically, proteoglycan fragment concentrations in knee joint fluid decreased with maturation, and were inversely correlated with the maturation stage of the rabbits (r = - 0.69). The relatively high proteoglycan fragment concentrations in young animals might be the result of a higher turnover rate of proteoglycans in growing articular cartilage. The stiffness of articular cartilage in the rabbit knee joint decreased with maturation and was associated with an increase of subchondral bone volume fraction, and on the same time a substantial change in subchondral morphology. The results suggest that cartilage mechanics may also depend on the structural characteristics of subchondral bone.

Cartilage repair in young rabbits showed a faster filling of an osteochondral defect and an earlier differentiation to hyaline-like cartilage than repairs in adult ones. The higher repair quality in young animals compared with the adults remained up to 48 weeks. Repairs in initially adolescent and adult animals showed furthermore signs of progressing degeneration between 12 and 48 weeks with decrease of the amount of hyaline-like cartilage in the tissue. However, irrespective of age, surface disruption of the repair was common, and no repair achieved regeneration to normal articular cartilage. The compressive stiffness of the repair tissues was always markedly softer compared with normal cartilage.

In preoperative joint fluid samples, TGF-b1 decreased with maturation, and was moderately correlated with the proteoglycan fragment concentrations. Shortly after trauma, the concentrations of both substances were found increased, which was followed by a decrease up to 3 months, and then again an increase up to one year. However, meanwhile proteoglycan fragment concentrations had similar magnitude irrespective of age, TGF-b1 concentrations never reached similarly high levels in adulthood as in infancy or adolescence. The cartilage adjacent to the defect had more signs for degeneration in younger rabbits. The similar patterns of TGF-b1 and proteoglycan fragment concentrations during postnatal maturation may reflect the stimulatory effect of TGF-b1 on proteoglycan synthesis. The higher TGF-b1 concentrations in younger animals may be a reason for their better healing capacity, but also for their higher susceptibility to osteoarthritic change compared with the adult animals

Key words: rabbit, development, maturation, knee joint, articular cartilage, osteochondral defect, cartilage repair, joint fluid, subchondral bone volume fraction, proteoglycan fragment, transforming growth factor-b, biomechanics, indentation, histology, histomorphometry.

Sports Medicine, Faculty of Health Sciences, Linköping University, 581 85, Linköping, Sweden,

ISBN 91-7219-063-9 ISSN 0345-0082