Destruction of hyaline cartilage in the sigmoid notch of the human ulna.
In an ulna from an adolescent a fossa nudata divided the articular surface of the sigmoid notch into olecranon and coronoid areas. In the floor of the fossa a layer of loose avascular pannus covered a thin layer of articular cartilage. The pannus appeared to have been formed by removal of chondroitin from the cartilage, freeing the cells and unmasking the fibres. Probably the change followed loss of contact between the articular cartilages of the sigmoid notch and trochlea during postnatal growth. (+info)
Regulation of chondrocyte differentiation by Cbfa1.
Cbfa1, a developmentally expressed transcription factor of the runt family, was recently shown to be essential for osteoblast differentiation. We have investigated the role of Cbfa1 in endochondral bone formation using Cbfa1-deficient mice. Histology and in situ hybridization with probes for indian hedgehog (Ihh), collagen type X and osteopontin performed at E13.5, E14.5 and E17.5 demonstrated a lack of hypertrophic chondrocytes in the anlagen of the humerus and the phalanges and a delayed onset of hypertrophy in radius/ulna in Cbfa1-/- mice. Detailed analysis of Cbfa1 expression using whole mount in situ hybridization and a lacZ reporter gene reveled strong expression not only in osteoblasts but also in pre-hypertrophic and hypertrophic chondrocytes. Our studies identify Cbfa1 as a major positive regulator of chondrocyte differentiation. (+info)
Radial club hand with absence of the biceps muscle treated by centralisation of the ulna and triceps transfer. Report of two cases.
Two children with radial club hand and absence of the biceps muscle were treated by centralisation of the ulna into the carpus and triceps transfer. The two operations were performed only a short time apart so that the period between the procedures could be used to stretch the triceps and to enable the children to adapt to an altered position of the wrist and to mobility of the elbow at one step and following a single period of plaster immobilisation. It is very likely that function is better than it would have been had the condition remained untreated. Before operation the children had only a crude hook function of the hand against the forearm and could not bring the hand to the mouth. Even if function is not much improved, the improvement in appearance is considerable and is by itself sufficient to justify the procedures. (+info)
Retinoid signaling is required for chondrocyte maturation and endochondral bone formation during limb skeletogenesis.
Retinoids have long been known to influence skeletogenesis but the specific roles played by these effectors and their nuclear receptors remain unclear. Thus, it is not known whether endogenous retinoids are present in developing skeletal elements, whether expression of the retinoic acid receptor (RAR) genes alpha, beta, and gamma changes during chondrocyte maturation, or how interference with retinoid signaling affects skeletogenesis. We found that immature chondrocytes present in stage 27 (Day 5.5) chick embryo humerus exhibited low and diffuse expression of RARalpha and gamma, while RARbeta expression was strong in perichondrium. Emergence of hypertrophic chondrocytes in Day 8-10 embryo limbs was accompanied by a marked and selective up-regulation of RARgamma gene expression. The RARgamma-rich type X collagen-expressing hypertrophic chondrocytes lay below metaphyseal prehypertrophic chondrocytes expressing Indian hedgehog (Ihh) and were followed by mineralizing chondrocytes undergoing endochondral ossification. Bioassays revealed that cartilaginous elements in Day 5.5, 8.5, and 10 chick embryo limbs all contained endogenous retinoids; strikingly, the perichondrial tissues surrounding the cartilages contained very large amounts of retinoids. Implantation of beads filled with retinoid antagonist Ro 41-5253 or AGN 193109 near the humeral anlagens in stage 21 (Day 3.5) or stage 27 chick embryos severely affected humerus development. In comparison to their normal counterparts, antagonist-treated humeri in Day 8.5-10 chick embryos were significantly shorter and abnormally bent; their diaphyseal chondrocytes had remained prehypertrophic Ihh-expressing cells, did not express RARgamma, and were not undergoing endochondral ossification. Interestingly, formation of an intramembranous bony collar around the diaphysis was not affected by antagonist treatment. Using chondrocyte cultures, we found that the antagonists effectively interfered with the ability of all-trans-retinoic acid to induce terminal cell maturation. The results provide clear evidence that retinoid-dependent and RAR-mediated mechanisms are required for completion of the chondrocyte maturation process and endochondral ossification in the developing limb. These mechanisms may be positively influenced by cooperative interactions between the chondrocytes and their retinoid-rich perichondrial tissues. (+info)
Bone-peg grafting for osteochondritis dissecans of the elbow.
In the treatment of osteochondritis dissecans involving the elbow, we have used a bone-peg graft taken from the proximal part of the ulna and inserted into the defect. Thirty-two patients were followed from 2 to 10.5 years. The graft was utilised in 20 elbows, and 6 of these also had concomitant removal of a loose body. Another 6 elbows had removal of a loose body only. Ten elbows were treated conservatively in 5 of these the outcome was unsatisfactory, including 4 in which a bone-peg graft was later necessary. The bone-peg graft gave the best short-term results. Bony union of the dissecans site and reconstitution of subchondral bone required an average of 6.5 months. In 15 patients followed for a minimum of 5 years, the bone-peg graft was effective in limiting the development of osteoarthritis. Bone-peg grafting is a reliable method for treating osteochondritis dissecans of the elbow. (+info)
The spectrum of mutations in TBX3: Genotype/Phenotype relationship in ulnar-mammary syndrome.
Ulnar-mammary syndrome (UMS) is a pleiotropic disorder affecting limb, apocrine-gland, tooth, hair, and genital development. Mutations that disrupt the DNA-binding domain of the T-box gene, TBX3, have been demonstrated to cause UMS. However, the 3' terminus of the open reading frame (ORF) of TBX3 was not identified, and mutations were detected in only two families with UMS. Furthermore, no substantial homology outside the T-box was found among TBX3 and its orthologues. The subsequent cloning of new TBX3 cDNAs allowed us to complete the characterization of TBX3 and to identify alternatively transcribed TBX3 transcripts, including one that interrupts the T-box. The complete ORF of TBX3 is predicted to encode a 723-residue protein, of which 255 amino acids are encoded by newly identified exons. Comparison of other T-box genes to TBX3 indicates regions of substantial homology outside the DNA-binding domain. Novel mutations have been found in all of eight newly reported families with UMS, including five mutations downstream of the region encoding the T-box. This suggests that a domain(s) outside the T-box is highly conserved and important for the function of TBX3. We found no obvious phenotypic differences between those who have missense mutations and those who have deletions or frameshifts. (+info)
Dynamic injury tolerances for long bones of the female upper extremity.
This paper presents the dynamic injury tolerances for the female humerus and forearm derived from dynamic 3-point bending tests using 22 female cadaver upper extremities. Twelve female humeri were tested at an average strain rate of 3.7+/-1.3%/s. The strain rates were chosen to be representative of those observed during upper extremity interaction with frontal and side airbags. The average moment to failure when mass scaled for the 5th centile female was 128+/-19 Nm. Using data from the in situ strain gauges during the drop tests and geometric properties obtained from pretest CT scans, an average dynamic elastic modulus for the female humerus was found to be 24.4+/-3.9 GPa. The injury tolerance for the forearm was determined from 10 female forearms tested at an average strain rate of 3.94+/-2.0%/s. Using 3 matched forearm pairs, it was determined that the forearm is 21% stronger in the supinated position (92+/-5 Nm) versus the pronated position (75+/-7 Nm). Two distinct fracture patterns were seen for the pronated and supinated groups. In the supinated position the average difference in fracture time between the radius and ulna was a negligible 0.4+/-0.3 ms. However, the pronated tests yielded an average difference in fracture time of 3.6+/-1.2 ms, with the ulna breaking before the radius in every test. This trend implies that in the pronated position, the ulna and radius are loaded independently, while in the supinated position the ulna and radius are loaded together as a combined structure. To produce a conservative injury criterion, a total of 7 female forearms were tested in the pronated position, which resulted in the forearm injury criterion of 58+/-12 Nm when scaled for the 5th centile female. It is anticipated that these data will provide injury reference values for the female forearm during driver air bag loading, and the female humerus during side air bag loading. (+info)
Transcription repression by Xenopus ET and its human ortholog TBX3, a gene involved in ulnar-mammary syndrome.
T box (Tbx) genes are a family of developmental regulators with more than 20 members recently identified in invertebrates and vertebrates. Mutations in Tbx genes have been found to cause several human diseases. Our understanding of functional mechanisms of Tbx products has come mainly from the prototypical T/Brachyury, which is a transcription activator. We previously discovered ET, a Tbx gene expressed in Xenopus embryos. We report here that ET is an ortholog of the human Tbx3 and that ET is a repressor of basal and activated transcription. Functional dissection of the ET protein reveals a novel transcription-repression domain highly conserved among ET, human TBX3, and TBX2. These results reveal a new transcription repressor domain, show the existence of a subfamily of transcription repressors in the Tbx superfamily, and provide a basis for understanding etiology of diseases caused by Tbx3 mutations. (+info)