Prenatal food restriction induces poor-quality articular cartilage in female rat offspring fed a post-weaning high-fat diet and its intra-uterine programming mechanisms.

Epidemiological data show that osteoarthritis (OA) is significantly associated with lower birth weight, and that OA may be a type of fetal-originated adult disease. The present study aimed to investigate the prenatal food-restriction (PFR) effect on the quality of articular cartilage in female offspring to explore the underlying mechanisms of fetal-originated OA. Maternal rats were fed a restricted diet from gestational day (GD) 11 to 20 to induce intra-uterine growth retardation. Female fetuses and female adult offspring fed a post-weaning high-fat diet were killed at GD20 and postnatal week 24, respectively. Serum and knee cartilage samples from fetuses and adult female offspring were collected and examined for cholesterol metabolism and histology. Fetal serum corticosterone and insulin-like growth factor-1 (IGF-1) in the PFR group were lower than those of the control, but the serum cholesterol level was not changed. The lower expression of IGF-1 in the PFR group lasted into adulthood. The expression of extracellular matrix (ECM) genes, including type II collagen, aggrecan and cholesterol efflux genes including liver X receptor, were significantly induced, but the ATP-binding-cassette transporter A1 was unchanged. PFR could induce a reduction in ECM synthesis and impaired cholesterol efflux in female offspring, and eventually led to poor quality of articular cartilage and OA.

Signaling pathways in human skeletal dysplasias.

Human skeletal dysplasias are disorders that result from errors in bone, cartilage, and joint development. A complex series of signaling pathways, including the FGF, TGFbeta, BMP, WNT, Notch, and Hedgehog pathways, are essential for proper skeletogenesis, and human skeletal dysplasias are often a consequence of primary or secondary dysregulation of these pathways. Although these pathways interact to regulate bone, cartilage, and joint formation, human genetic phenotypes point to the predominant action of specific components of these pathways. Mutations in the genes with a role in metabolic processing within the cell, the extracellular matrix, and transcriptional regulation can lead to dysregulation of cell-cell and cell-matrix signaling that alters tissue patterning, cell differentiation, proliferation, and apoptosis. We propose a morphogen rheostat model to conceptualize how mutations in different metabolic processes can lead to the integration of differential signaling inputs within a temporal and spatial context to generate apparently divergent skeletal phenotypes.

Effect of in ovo immobilization on development of chick hind-limb articular cartilage: an evaluation using micro-MRI measurement of delayed gadolinium uptake.

To examine the effect of immobilization on the development of articular cartilage, we assessed glycosaminoglycan (GAG) content in the chick articular surface by delayed gadolinium-enhanced MRI of cartilage (dGEMRIC). Chick embryos were paralyzed by decamethonium bromide (DMB) from day 10 to either day 13 or day 16. The GAG content of the chick knee was compared with that of nonparalyzed chick embryos. Histologic analysis was unable to quantify GAG content; however, dGEMRIC demonstrated that GAG content was higher in the femoral condyles of the nonparalyzed embryos on day 13, and on day 16 the GAG content was lower in both the femoral condyles and the tibial plateaus of the nonparalyzed embryos. These results suggest that paralysis delays embryonic hind-limb development. Osteoblastic activity at the cartilage canal, as demonstrated by staining for alkaline phosphatase (ALP), was present only in the nonparalyzed chick embryos on day 16. The GAG content of the cartilage decreased when the cartilage canals began to form on day 16. The effect of immobilization on hind-limb development was indicated by the differences in the GAG content of the cartilage anlage measured by dGEMRIC in the developing knee joint of paralyzed and nonparalyzed embryonic chicks.

Brachyury and chordoma: the chondroid-chordoid dilemma resolved?

Chordoma, and its relationship to the notochord, has intrigued many researchers over the last two centuries. In particular, the morphological overlap with cartilaginous tumours is striking, and developmental biology has shown a tight relationship between cartilage and the notochord. This is reflected in the expression of common genes in chordoid and chondroid tumours. Wide gene expression analyses have led to the identification of key molecules that might play a crucial role in the pathogenesis of chordoma. Brachyury, a key factor in notochord fate, is significantly differentially expressed in chordoma. This not only gives insight into the histogenesis of this tumour but may also point towards new diagnostic tools in the differential diagnosis between chordoid and chondroid tumours.

Prenatal development around the sustentaculum tali and its relation to talocalcaneal coalitions.

Twenty cartilaginous talocalcaneal bridges were found in 16 cases among 142 feet from 119 embryos and fetuses ranging from 7 to 20 weeks. The cartilaginous bridges were mainly located extraarticularly between the posteromedial portion of the sustentaculum tali and the corresponding part of the talus. The incidence of talocalcaneal bridges was high in the prenatal period, especially during the ninth and tenth week; it was much less common in older specimens. This condition is attributed to either failure of or delay in differentiation of mesenchymal tissue into more specialized tissue between the posterior portion of sustentaculum tali and the corresponding part of the talus during the 7 1/2-8 1/2 postovulatory weeks.

[Morphological study of the epiphyseal cartilage in cartilage matrix deficiency (CMD) mouse--a consideration on the roles and functions of cartilage-specific proteoglycan].

Epiphyseal cartilages in mouse with cartilage matrix deficiency due to genetic failure to synthesize cartilage-characteristic proteoglycan were examined under light and electron microscope. Chondrogenesis and proliferation of chondrocytes seemed to occur, though extracellular matrix was small in amount and chondrocytes were packed closely without consistent orientation. In diaphysis, hypertrophic change of chondrocytes and perichondral ossification were observed. In the epiphysis, there was neither zone formation nor column formation, but hypertrophic chondrocytes and calcification in matrix were observed in the area adjacent to the bone shaft. Electron microscopy showed dilatation of rough endoplasmic reticulum, swelling of mitochondria and a large amount of lipid deposition in the chondrocyte. In the cartilage matrix, it was characteristic that a large number of thick collagen fibrils was arranged in parallel and few matrix granule was seen. These findings suggested that cartilage-characteristic proteoglycan was not essential for chondrogenesis, proliferation of chondrocytes and ossification, but were important for cytodifferentiation and chondrocyte activity.