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)
Delayed osteon formation in long-bone diaphysis of an 11-year-old giant cow with dermal dysplasia.
The transverse sections of radius diaphysis in an 11-year-old giant Holstein cow with dermal dysplasia of a collagen disorder-related skin fragility (Cow 1), probably based on increasing turnover of the dermal collagen as reported previously, were morphologically and physico-chemically investigated. Cow 1 had about one and a half times as much as the body weight of normal Holstein cows, aged 5 to 6.5 years with stabilized growth. The bone samples were compared with those of a 12-year-old Holstein cow as controls (Cow 2). It has been reported that the long-bone diaphysis of young calves and some herbivorous dinosaurs are occupied with laminar bone showing a concentric appositional formation, and that such a laminar bone is characteristically seen during the growing period of some farm animals and large dogs that show very rapid growth rates. Cow 1 had a smaller number of osteons than Cow 2 in the outer-half layer of the diaphysis, and showed an intermediate type between Cow 2 and a 1-year-old Holstein ox in the entire layers, although their bone volumes were similar among them. There were no significant differences in Ca and P concentrations and the Vickers microhardness values between the bone matrix of Cow 1 and Cow 2. The bone-collagen fibrils of Cow 1 showed uneven diameters and a disordered arrangement. Thus, there may be some relation in collagen formation between the bone matrix of Cow 1 and the dermis. From the remaining volume of laminar bone, Cow 1, aged 11 years, had probably shown growth until quite recently, so that we consider that Cow 1 became a giant animal, in the same way as some herbivorous dinosaurs. (+info)
Mechanical function as an influence on the structure and form of bone.
Rosette strain gauges were attached to the cranial and caudal aspects of the proximal half of the radius in eight skeletally mature female sheep; The sheep's radius has a slight cranially convex curvature. During walking it was deformed so that the cranial surface was subjected to tension aligned along the bone's lon axis, and the caudal surface to compression similarly aligned. The compressive strain on the caudal aspect of the bone was consistently larger (X 1-9) than the tensile strain on the cranial aspect. The thickness of the cortex did not reflect this difference but in younger animals the process of osteonal remodelling seemed further advanced in the cortex which was customarily subject to the larger deformation. The relevance of these findings is discussed in relation to the technique of internal fixation and to our understanding of the basis of the mechanical adaptability of bone. (+info)
Excision of the head of the radius in rheumatoid arthritis.
The results of excision of the head of the radius in forty-four elbows affected by rheumatoid arthritis are presented. Relief of pain was obtained in 90 per cent and an increase in the range of flexion and extension was seen in 70 per cent. Involvement of the humero-ulnar joint seen radiologically is no contra-indication to the operation; simple excision of the radial head often gives gratifying results; In our experience the relief of pain and increased range of movement have greatly reduced the need for total replacement arthroplasty. (+info)
Tomographical description of tennis-loaded radius: reciprocal relation between bone size and volumetric BMD.
Effects of long-term tennis loading on volumetric bone mineral density (vBMD) and geometric properties of playing-arm radius were examined. Paired forearms of 16 tennis players (10 women) and 12 healthy controls (7 women), aged 18-24 yr, were scanned at mid and distal site by using peripheral quantitative computerized tomography. Tomographic data at midradius showed that tennis playing led to a slight decrease in cortical vBMD (-0.8% vs. nonplaying arm, P < 0. 05) and increase both in periosteal and endocoritcal bone area (+15. 2% for periosteal bone, P < 0.001; and +18.8% for endocortical bone, P < 0.001). These data suggest that, together with an increase in cortical thickness (+6.4%, P < 0.01), cortical drift toward periosteal direction resulted in improvement of mechanical characteristics of the playing-arm midradius. Enlargement of periosteal bone area was also observed at distal radius (+6.8%, P < 0.01), and the relative side-to-side difference in periosteal bone area was inversely related to that in trabecular vBMD (r = -0.53, P < 0.05). We conclude that an improvement of mechanical properties of young adult bone in response to long-term exercise is related to geometric adaptation but less to changes in vBMD. (+info)
Maturational disturbance of chondrocytes in Cbfa1-deficient mice.
Cbfa1, a transcription factor that belongs to the runt-domain gene family, plays an essential role in osteogenesis. Cbfa1-deficient mice completely lacked both intramembranous and endochondral ossification, owing to the maturational arrest of osteoblasts, indicating that Cbfa1 has a fundamental role in osteoblast differentiation. However, Cbfa1 was also expressed in chondrocytes, and its expression was increased according to the maturation of chondrocytes. Terminal hypertrophic chondrocytes expressed Cbfa1 extensively. The significant expression of Cbfa1 in hypertrophic chondrocytes was first detected at embryonic day 13.5 (E13.5), and its expression in hypertrophic chondrocytes was most prominent at E14.5-16.5. In Cbfa1-deficient mice, whose entire skeleton was composed of cartilage, the chondrocyte differentiation was disturbed. Calcification of cartilage occurred in the restricted parts of skeletons, including tibia, fibula, radius, and ulna. Type X collagen, BMP6, and Indian hedgehog were expressed in their hypertrophic chondrocytes. However, osteopontin, bone sialoprotein, and collagenase 3 were not expressed at all, indicating that they are directly regulated by Cbfa1 in the terminal hypertrophic chondrocytes. Chondrocyte differentiation was severely disturbed in the rest of the skeleton. The expression of PTH/PTHrP receptor, Indian hedgehog, type X collagen, and BMP6 was not detected in humerus and femur, indicating that chondrocyte differentiation was blocked before prehypertrophic chondrocytes. These findings demonstrate that Cbfa1 is an important factor for chondrocyte differentiation. (+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)
The effect of dietary calcium intake on bone mineral density in healthy adolescent girls and young women in southern Italy.
BACKGROUND: The association between forearm bone mineral areal density (BMD) and dietary calcium, anthropometric characteristics, puberty, and physical activity was studied for the first time in 200 girls (aged 11-15 years) and 100 women (aged 20-23 years) living in Southern Italy. METHODS: The BMD was assessed by dual energy x-ray absorptiometry at ultradistal (ud) and proximal (pr) radial sites and dietary calcium was evaluated using Food Frequency Questionnaires and detailed 3-day food records. RESULTS: For population samples grouped according to low and high calcium intake levels, forearm densities were quite similar among both girls and women. Independently of calcium intake, girls displayed strong correlations between ud/pr-BMD and age, bone age, weight, height and BMI. Furthermore, in girls of similar age and BMI, radial densities were substantially increased following menarche. Positive relationships between weight, BMI and both ud/pr-BMD were only evident in women with high calcium intake. CONCLUSIONS: This study showed that different calcium intake values do not appear to affect forearm mineral densities at the ages investigated, however puberty represents the major event in radial bone mass acquisition during adolescence. (+info)