Experimental Research Of The Sequence And Reversibility Of Femoral Head Cartilage Degeneration In The Acetabular Dysplasia

[Background and Object]Developmental dysplasia of the hip (DDH) is one of the common deformities of limbs in children. Most of DDH patients were diagnosed earlierly now, because of early screening during infant. Even the hip development improve after close or open reduction, there are still around 70% patients suffering from residual acetabular dysplasia(RAD), which is potential cause of osteoarthritis(OA) when they are adults. Controversy always exists in terms of the most optimalized age to treat RAD. So far it is unknown that whether the pathophysiological changes in RAD cartilage can be reversible or not. Our previous data suggested that the degeneration of acetabular cartilage in acetabular dysplasia (AD) was time-dependent and reversible. But the changes of femoral head cartilage and the sequence and reversibility of the changes in AD are still unknown. So histomorphological changes, type I collagen and matrix metalloproteinase-13(MMP-13) of femoral head cartilages of serial immature rabbit AD models were observed in this study, in order to study the relevance between AD and OA, and to provide theory evidence for choosing the correct age for treating AD in children by observing the time point of reversibility of femoral head cartilage degeneration in AD.[Methods]Twenty seven 5-week-old New Zealand rabbits were randomly divided into three groups, namely A, B, C. And every group owned 9 rabbits. The left hind limb as the experimental side, which was given cast immobilization, maintaining knee extended and hip flexed for 2,4,6 weeks for each group respectively. The right hind limb served as the control side with no treatment. The anteroposterior pelvic radiograph of all rabbits were taken after 2 weeks cast immobilization. The results shows AD models were established. Five rabbits were sacrificed from each group after achieving their own casting time, composing the immature groups a,b and c. And the other four were given cast removal and were sacrificed at 6 months old, composing the mature groups A,B and C. The medial and lateral parts of femoral head cartilages were observed respectively. The morphology of femoral head cartilages was observed using HE staining, and the modified Mankin scores were gotten according to the morphology. Expression of type I collagen and Matrix metalloproteinase-13 (MMP-13) in femoral head cartilages were detected by the Immunohistochemical staining (IHC). Using Image-Pro Prus 6.0 to measure the integrated optical density(IOD). Stata 7 was adopted for statistics. Using two samples t test to compare experimental groups with control groups and medial parts with lateral parts.[Results]1. Histomorphological study and modified Mankin scores:Articular cartilages on control sides had smooth surfaces and tide lines were smooth in immature group a,b and c. On experimental side number of cartilage cells increased in immature group a; Tide line was blurred in immature group b; Cartilage had slightly irregular surface, cartilage cell number increased and a few cell clusters formed in immature group c. No significant difference of the modified Mankin scores in immature group a, b and c was found between experimental side and control side, nor did it between medial part and lateral part. In mature models, articular cartilages had slightly irregular surface, tide lines were blurred and interrupted both on control side and on experimental side in group A and B. No significant difference of the modified Mankin scores in group A and B was found between experimental side and control side, nor did it between medial parts and lateral parts. In mature group C cartilage surfaces were irregular, and there were a few hiatuses in the surfaces on experimental sides, cartilage cell number increased greatly, and the array of cells was disordered; Cell clusters were found frequently on experimental side. Tide lines were blurred. The modified Mankin score in group C experimental side was higher (P< 0.01). But no significant difference was found between medial part and lateral part.2. The expression of type I collagen in femoral head cartilage of the ADType I collagen was expressed in cytochylema in cartilage cells. In immature groups, expression of type I collagen increased gradually after 2,4,6-weeks immobilization. But no significant difference was found between experimental side and control side, nor did it between medial part and lateral part in group a and b. In group c, expression of type I collagen in experimental side is higher both in medial part and in lateral part (lateral part P=0.0013, medial part P=0.0201), and it is highe in lateral part than that in medial part in experimental side (P=0.0185). In mature groups, no significant difference was found between experimental side and control side, nor did it between medial part and lateral part in group A and B. Expression of type I collagen in experimental side is higher both in medial part and in lateral part (lateral part P=0.0004, medial part P=0.0083), and it is higher in lateral part in experimental side (P=0.0043) in group C.3. The expression of MMP-13 in femoral head cartilage of the ADMMP-13 was expressed in cytochylema in cartilage cells. In immature groups, expression of MMP-13 increased gradually after 2,4,6-weeks immobilization. No significant difference was found between experimental side and control side, nor did it between medial part and lateral part in group a. Expression of MMP-13 in experimental side was higher both in medial part and in lateral part (P<0.01, lateral part of group c P<0.05), but there was no significant difference between medial part and lateral part both in group b and in group c. In mature groups, no significant difference was found between experimental side and control side, nor did it between medial part and lateral part in group A. Expression of MMP-13 in experimental side was higher only in lateral part (P=0.0067). In medial part no significant difference was found in group B. Expression of MMP-13 in experimental side was higher both in medial part and in lateral part (lateral part P=0.0118, medial part P=0.044), but there was no significant difference between medial part and lateral part in group C.[Conclusions]1. Degeneration of femoral head cartilage in the acetabular dysplasia is sequential, and it is reversible in some stage.2. The expression of type I collagen and MMP-13 in femoral head cartilage in AD is higher when cartilage degenerated. MMP-13 may be a more sensitive monitor indicating cartilage degeneration.3. The difference of mechanical stress between medial part and lateral part in femoral head may cause difference of cartilage degeneration in some stage.