Association between expression of the Bone morphogenetic proteins 2 and 7 in the repair of circumscribed cartilage lesions with clinical outcome

<p>Abstract</p> <p>Background</p> <p>Although there is much known about the role of BMPs in cartilage metabolism reliable data about the <it>in vivo </it>regulation in natural and surgically induced cartilage repair are still missing.</p> <p>Methods</p> <p>Lavage fluids of knee joints of 47 patients were collected during surgical therapy. 5 patients had no cartilage lesion and served as a control group, the other 42 patients with circumscribed cartilage defects were treated by microfracturing (19) or by an Autologous Chondrocyte Implantation (23). The concentrations of BMP-2 and BMP-7 were determined by ELISA. The clinical status was evaluated using the IKDC Score prior to and 1 year following the operation.</p> <p>Results</p> <p>High level expression in the control group was found for BMP-2, concentrations of BMP-7 remained below detection levels. No statistical differences could be detected in concentrations of BMP-2 or BMP-7 in the lavage fluids of knees with cartilage lesions compared to the control group. Levels of BMP-7 did not change after surgical cartilage repair, whereas concentrations of BMP-2 statistically significant increased after the intervention (p < 0.001). The clinical outcome following cartilage regenerating surgery increased after 1 year by 29% (p < 0.001). The difference of the IKDC score after 1 year and prior to the operation was used to quantify the degree of improvement following surgery. This difference statistically significant correlated with initial BMP-2 (R = 0.554, p < 0.001) but not BMP-7 (R = 0.031, n.s.) levels in the knee joints.</p> <p>Conclusions</p> <p>BMP-2 seems to play an important role in surgically induced cartilage repair; synovial expression correlates with the clinical outcome.</p

Deficient antibody formation in the bone marrow of nude mice

The bone marrow of young adult nude mice was investigated as a site of antibody formation after intravenous immunization with the thymus-independent antigen Escherichia coli lipopolysaccharide (LPS). Mice heterozygous for the nu-gene were found to be capable of a plaque-forming cell (PFC) response in both spleen and bone marrow after primary and secondary immunization with LPS. Primary immunization of nude mice with LPS induced a normal PFC response in the spleen, but did not evoke the appearance of PFC in the bone marrow. During the secondary response the nude mice did show PFC activity in the bone marrow, but at a much lower level than their heterozygous littermates. At all time points after secondary immunization the number of splenic PFC was higher in nude mice than in the control mice. Determination by immunofluorescence of cells containing cytoplasmic immunoglobulin (C-Ig cells) in the bone marrow of young adult nonimmune nude and heterozygous mice, revealed a three times higher number of C-IgM cells in the bone marrow of the heterozygous thymus-bearing mice. On the other hand, the number of splenic C-IgM cells was higher in the nude mice than in their heterozygous littermates. These results suggest that the presence of the thymus facilitates the appearance of mature antibody-forming cells in the bone marrow of young adult mice, irrespective of whether the generation of these cells is initiated by so called thymus-dependent or thymus-independent antigens

Frequencies of background cytoplasmic Ig-containing cells in various lymphoid organs of athymic asplenic (lasat), athymic, asplenic and normal BALB/c mice

The frequency of immunoglobulin-containing plasma blasts and plasma cells (C-Ig cells) was determined by means of immunofluorescence in various lymphoid organs of hereditarily athymic asplenic (lasat), athymic (nude), asplenic (all on a BALB/c background) and normal BALB/c mice. Two age groups were tested, namely 8 and 14 weeks. The total number of C-Ig cells in spleen, bone marrow, lymph nodes and Peyer's patches together was the largest in the normal BALB/c mice, the smallest in the lasat mice, and intermediate in the athymic mice and the asplenic mice. The mice of all four groups had more C-Ig cells at the age of 14 weeks than at the age of 8 weeks. In 8-week-old BALB/c mice and in athymic nude mice most C-Ig cells were located in the spleen. In lasat mice and in thymus-bearing asplenic mice the bone marrow was the major site of localization of C-Ig cells. In all four groups of mice the number of C-Ig cells increased considerably with age, especially in the bone marrow. In athymic mice, whether asplenic or not, C-Ig cell numbers in the Peyer's patches were deficient. The percentage distribution of C-IgM, C-IgG1, C-IgG2, C-IgG3 and C-IgA cells was different for different lymphoid organs, and was dependent on both the spleen and the thymus. In normal BALB/c mice C-IgM cells were the most frequent in the spleen, whereas the other classes of C-Ig cells were the most frequent in the other lymphoid organs. In absolute numbers, C-IgM cells were the most numerous in the two groups of eusplenic mice, and C-IgG and C-IgA cells in the two groups of euthymic mice

Influence of muscular activity on local mineralization patterns in metatarsals of the embryonic mouse

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Influence of muscular activity on local mineralization patterns in metatarsals of the embryonic mouse

This study addressed the theory that local mechanical loading may influence the development of embryonic long bones. Embryonic mouse metatarsal rudiments were cultured as whole organs, and the geometry of the primary ossification center was compared with that of rudiments that had developed in utero. The mineralization front in vivo was found to be nearly straight, whereas in vitro it acquired a more convex shape due to a slower mineralization rate at the periphery of the mineralized cylinder. A poroelastic finite element analysis was performed to calculate the local distributions of distortional strain and fluid pressure at the mineralization front in the metatarsal during loading in vivo as a result of muscle contractions in the embryonic hindlimbs. The distribution of fluid pressure from the finite element analysis could not explain the difference in mineralization shape. The most likely candidate for the difference was the distortional strain, resulting from muscle contraction, which is absent in vitro, because its value at the periphery was significantly higher than in the center of the tissue. Without external loads, the mineralization process may be considered as pre-programmed, starting at the center of the tissue and resulting in a spherical mineralization front. Strain modulates the rate of the mineralization process in vivo, resulting in the straight mineralization front. These results confirm that disturbances in muscle development are likely to produce disturbed mineralization patterns, resulting in a disordered osteogenic process