tetracycline and Osteosclerosis

The DeltaFosB isoforms are naturally occurring AP-1 family members that increase bone volume via a cell-autonomous effect on osteoblastic bone formation. Mice overexpressing DeltaFosB demonstrate a very high level of bone formation, resulting in a progressive osteosclerosis. Despite the linkage of bone formation and resorption in physiological systems, no alteration in bone resorption was detected in mice overexpressing DeltaFosB. To determine whether altering DeltaFosB expression can regulate bone formation independently of bone resorption in adult mice, we used the Tet-Off-inducible transgene system to induce or block transgenic DeltaFosB overexpression and thereby regulate bone formation in vivo. Overexpression of DeltaFosB after skeletal maturity increased trabecular bone volume by increasing bone formation, again without altering bone resorption, indicating that developmental DeltaFosB overexpression is not required for the osteosclerotic phenotype. Similarly, switching off DeltaFosB overexpression after osteosclerosis had developed led to a marked decrease in bone formation and loss of bone mass such that trabecular bone volume approached normal levels. Despite this dramatic reduction, no alteration in bone resorption was detected. These results clearly demonstrate that DeltaFosB regulates bone formation and bone mass in adult mice with no effect on bone resorption.

Topics: Animals; Bone Density; Bone Resorption; Doxycycline; Female; Gene Expression Regulation; Mice; Mice, Transgenic; Osteogenesis; Osteosclerosis; Ovariectomy; Proto-Oncogene Proteins c-fos; Tetracycline; Transcription Factor AP-1

The patients with late osteoarthritis of the knee joint were given oral tetracycline to label the newly formed bone tissues before they were subjected to high tibial osteotomies or knee replacements. During the operation, the sclerotic subchondral bone tissue of the tibia and/or femur were procured. The bone specimens were processed into undecalcified sections and studied under fluorescence microscope. Apart from the autofluorescence of the trabeculae, strips of golden green labelled fluorescence of high intensity were noted along their peripheries, indicating that there were formatting and deposition of new bone along the periphery of the trabeculae. These new bone tissues were produced by the osteoblasts abutting the trabecular periphery. In the fatty tissues of the marrow interstices between the trabeculae, scattered dots and small flakes of golden green labelled fluorescence emerged at first. Then the labelled-fluorescent dots and flakes agglomerated into large pieces of more intense fluorescence with concomitant decrease in fatty tissues. Eventually, these large pieces of labelled fluorescence fused with those of the trabeculae and there was a further decrease in fatty tissues. These findings suggested that the formation and deposition of new bone tissues in the marrow interstices proceeded according to above three stages. The new bone tissues were produced by marrow stromal cells. The two kinds of new bone tissues increased the bone mass and rendered sclerotic changes in upper end of the tibia and lower end of the femur in osteoarthritis of knee joint.

Topics: Cartilage, Articular; Humans; Knee Joint; Microscopy, Fluorescence; Osteoarthritis; Osteosclerosis; Tetracycline

Topics: Bone Regeneration; Fluorescence; Fractures, Bone; Fractures, Ununited; Humans; Microscopy; Microscopy, Fluorescence; Osteogenesis; Osteosclerosis; Tetracycline