Jortikka M O, Inkinen R I, Tammi M I, Parkkinen J J, Haapala J, Kiviranta I, Helminen H J, Lammi M J
Department of Anatomy, University of Kuopio, Finland.
Ann Rheum Dis. 1997 Apr;56(4):255-61. doi: 10.1136/ard.56.4.255.
The capacity of articular cartilage matrix to recover during 50 weeks of remobilisation after an atrophy caused by 11 weeks of immobilisation of the knee (stifle) joint in 90 degrees flexion starting at the age of 29 weeks, was studied in young beagle dogs.
Proteoglycan concentration (uronic acid) and synthesis ([35S]sulphate incorporation) were determined in six and three knee joint surface locations, respectively. Proteoglycans extracted from the cartilages were characterised by chemical determinations, gel filtration, and western blotting for chondroitin sulphate epitope 3B3.
The proteoglycan concentrations that were reduced in all sample sites immediately after the immobilisation, remained 14-28% lower than controls after 50 weeks of remobilisation in the patella, the summit of medial femoral condyle, and the superior femoropatellar surface. In the contralateral joint, there was a 49% increase of proteoglycans in the inferior femoropatellar surface after remobilisation, while a 34% decrease was simultaneously noticed on the summit of the medial femoral condyle. Total proteoglycan synthesis was not significantly changed after immobilisation or 50 weeks' remobilisation in the treated or contralateral joint, compared with age matched controls. The chondroitin 6- to 4- sulphate ratio was reduced by immobilisation both in the radioactively labelled and the total tissue proteoglycans. In the remobilised joint, this ratio was restored in femur, while in tibia it remained at a level lower than controls. Neither immobilisation nor remobilisation induced epitopes recognised by the monoclonal antibody 3B3 on native (undigested) proteoglycans.
These results show that the depletion of proteoglycans observed after 11 weeks of immobilisation was not completely restored in certain surface sites after 50 weeks of remobilisation. The significant changes that developed in the contralateral joint during the remobilisation period give further support to the idea that a permanent alteration of matrix metabolism results even from a temporary modification of loading pattern in immature joints.
在年轻的比格犬中,研究膝关节在29周龄时以90度屈曲固定11周导致萎缩后,关节软骨基质在50周活动恢复期间的恢复能力。
分别在六个和三个膝关节表面位置测定蛋白聚糖浓度(糖醛酸)和合成([35S]硫酸盐掺入)。从软骨中提取的蛋白聚糖通过化学测定、凝胶过滤和针对硫酸软骨素表位3B3的蛋白质印迹进行表征。
固定后所有样本部位的蛋白聚糖浓度立即降低,在髌骨、股骨内侧髁顶部和股骨髌上表面活动恢复50周后,仍比对照组低14%-28%。在对侧关节,活动恢复后股骨髌下表面的蛋白聚糖增加了49%,而股骨内侧髁顶部同时出现了34%的下降。与年龄匹配的对照组相比,固定或50周活动恢复后,治疗关节或对侧关节的总蛋白聚糖合成没有显著变化。固定使放射性标记的和总组织蛋白聚糖中的硫酸软骨素6-4硫酸盐比率降低。在活动恢复的关节中,股骨中的该比率恢复,而胫骨中的该比率仍低于对照组水平。固定和活动恢复均未在天然(未消化)蛋白聚糖上诱导单克隆抗体3B3识别的表位。
这些结果表明,固定11周后观察到的蛋白聚糖耗竭在活动恢复50周后,某些表面部位并未完全恢复。活动恢复期间对侧关节发生的显著变化进一步支持了这样一种观点,即即使是未成熟关节负荷模式的暂时改变也会导致基质代谢的永久性改变。