Early Cartilage Degeneration in a Rat Experimental Model of Developmental Dysplasia of the Hip

Abstract

Osteoarthritis (OA) is a common long-term complication of developmental dysplasia of the hip (DDH) that is associated with a higher incidence of OA. In addition, the age of onset of OA in DDH patients is significantly younger than in the general population. In order to investigate the early degeneration in DDH cartilage, we used a rat DDH model that was established by the straight-leg swaddling position. The hips were isolated from the DDH model rats and an untreated control group at postnatal weeks 2, 4, 6, and 8. Histology and proteoglycan levels were observed in articular cartilage using Safranin O staining. Biomarkers of cartilage degeneration, including type X collagen and matrix metalloproteinase (MMP)-13, were assessed using immunohistochemistry and quantitative real-time polymerase chain reaction. In addition, expressions of ADAMTS-4 and ADAMTS-5 were studied using quantitative real-time polymerase chain reaction at different ages. DDH rats showed decreased proteoglycans and derangement of chondrocytes when compared with the control group. Collagen X and MMP-13 expressions were higher in the superficial zone of DDH rats than in that of controls (p < 0.05), and the increase was age-dependent. mRNA expression of Collagen X and MMP-13 showed similar results (p < 0.05). A significant increase in mRNA expression of ADAMTS-5 was found in the DDH model cartilage at 8 weeks (p < 0.05). However, no change was observed in ADAMTS-4 expression. This study shows that degenerative cartilage changes occur at an early stage in the rat DDH model and become aggravated with age.

Rotational Acetabular Osteotomy for Osteoarthritis with Acetabular Dysplasia

“…These differences may have appeared in the long-term follow-up because the joint space had already narrowed before surgery in patients with initial osteoarthritis and because there were changes in the femoral head cartilage 30,31 . We found that if postoperative congruency was excellent or good, osteoarthritis did not progress readily, even over the long term.…”

Novel mutation in Teneurin 3 found to co‐segregate in all affecteds in a multi‐generation family with developmental dysplasia of the hip

“…It is not unusual to find examples of non‐penetrance in a complex disorder like DDH as environmental factors are known to affect the phenotype. Indeed, the DDH affected South African family studied by Roby and his colleagues and families investigated by other researchers have shown non‐penetrance …”

“…Specifically, expression was strongest in the fibrous layer which is thought to be the source of chondrogenic cells. Importantly this expression appeared to be stage specific as it was expressed at a lower level in mature articular chondroctyes and was absent in hypertrophic chondrocytes …”

“…Indeed, the DDH affected South African family studied by Roby and his colleagues and families investigated by other researchers have shown non-penetrance. 14,15,26,27 Recently it has been reported that a South African family suffering from Beukes developmental dysplasia of the hip is caused by a missense mutation in the ubiquitin-fold modifier 1-specific peptidase 2 ((UFSP2) gene which resides at 4q35.1, a location near the TENM3 gene. 28 There are a number of phenotypic features that differentiate the family reported here from the South African one.…”

Increasing substance P levels in serum and synovial tissues from patients with developmental dysplasia of the hip (DDH)

“…The incidence rate of female and male with DDH is approximately 4–10:1 in different countries [1,2]. The pathogenesis of DDH includes: susceptibility to the X chromosome, genetic mutation, breech presentation, swaddling position, and mechanical factors of hip joint during acquired environment [3-5]. Besides, DDH is often accompanied by series of morphological and anatomic changes in hip joint, which bring about joint space narrowing, articular surface abrasion, secondary osteoarthritis, synovial hyperplasia, and cystic change in subchondral bone [6,7].…”