oxytetracycline--anhydrous and Osteoarthritis

To effectively treat degenerative joint diseases including osteoarthritis (OA), small chemical compounds need to be developed that can potently induce chondrogenic differentiation without promoting terminal differentiation. For this purpose, we screened natural and synthetic compound libraries using a Col2GFP-ATDC5 system and identified oxytetracycline (Oxy) as a chondrogenic compound. Oxy induced cartilaginous matrix synthesis and mRNA expressions of chondrocyte markers in ATDC5 cells. In addition, Oxy suppressed mineralization and mRNA expressions of terminal chondrocyte differentiation markers in ATDC5 cells, primary chondrocytes, and cultured metatarsal bones. Oxy's induction of Col2 mRNA expression was decreased by the addition of Noggin and was increased by the addition of BMP2. Furthermore, Oxy increased mRNA expression of Id1, Bmp2, Bmp4, and Bmp6. These data suggest that Oxy induces chondrogenic differentiation in a BMP-dependent manner and suppresses terminal differentiation. Oxy may be useful for treatment of OA and also for regeneration of cartilage tissue.

Topics: Animals; Antigens, Differentiation; Bone Morphogenetic Proteins; Cell Differentiation; Cell Line; Cells, Cultured; Chondrocytes; Collagen Type II; Drug Evaluation, Preclinical; Embryo, Mammalian; Gene Expression Regulation; High-Throughput Screening Assays; Inhibitor of Differentiation Protein 1; Metatarsal Bones; Mice; Mice, Inbred C57BL; Osteoarthritis; Osteogenesis; Oxytetracycline; RNA, Messenger; Small Molecule Libraries; Tissue Culture Techniques

The effect of immobilization on bone formation in the knee and hip was studied by means of oxytetracycline. One leg of 11 growing and 13 adult rabbits was immobilized so that the knee was held in extension but the hip was free. In the knee, degenerative changes developed consistently with a severity proportional to the length of the immobilization time. In most of the rabbits given oxytetracycline 1-13 days before they were killed considerably more oxytetracycline was incorporated in the bone in the immobilized knee region and slightly more in the hip region of the same leg than in the corresponding areas of the other leg. This indicates an increased turnover of bone tissue in the immobilized leg compared with the non-immobilized leg.

Topics: Animals; Hip Joint; Immobilization; Knee Joint; Osteoarthritis; Osteogenesis; Oxytetracycline; Rabbits; Radiography

Multiple doses of oxytetracycline were administered at regular but different intervals to groups of patients undergoin orthopaedic surgery. It was found that doses of the drug were incorporated at bone growth sites most frequently if the intervals between those doses were 3 or 6 days. This suggests a biorhythm in human bone growth with a periodicity of 3 days: this biorhythm may be altered by hormones or drugs.

Topics: Adult; Aged; Arthritis, Rheumatoid; Female; Femur Neck; Fractures, Bone; Humans; Ilium; Kinetics; Male; Microscopy, Fluorescence; Middle Aged; Osteoarthritis; Osteogenesis; Oxytetracycline; Periodicity; Tibia; Time Factors

Topics: Adult; Aged; Arthritis, Rheumatoid; Bone Matrix; Cadaver; Cartilage, Articular; Female; Femoral Fractures; Femoral Neck Fractures; Femur Head; Fractures, Spontaneous; Humans; Male; Microscopy, Fluorescence; Middle Aged; Osteoarthritis; Oxytetracycline

Charnley low-friction arthroplasty was performed on 352 osteoarthritic hips, usually because of severe pain. Three hundred and twenty hips were reviewed at a special follow-up clinic or by postal questionnaire. After operation 89% of hips were pain-free or caused only occasional discomfort, and in 76% there was an increased range of movement. Of those patients actually seen for review 79% were judged to have a good or excellent result. The most frequent single complication was deep infection, which occurred in 5.3% of hips.

Topics: Acetabulum; Adult; Aged; Ampicillin; Arthroplasty; Cloxacillin; Femur; Follow-Up Studies; Hip; Hip Dislocation; Humans; Joint Prosthesis; Middle Aged; Movement; Osteoarthritis; Oxytetracycline; Pain; Postoperative Care; Postoperative Complications; Surgical Wound Infection