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Leptin treatment induces loss of bone marrow adipocytes and increases bone formation in leptin-deficient ob/ob mice.

Author	Mark W Hamrick, Mary Anne Della-Fera, Yang-Ho Choi, Catherine Pennington, Diane Hartzell, Clifton A Baile
Citation Information	Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 20:994-1001 (2005)
Keywords	BMIA, Adipocytes, Animals, Apoptosis, Bone Density, Bone Development, Bone Marrow Cells, Bone and Bones, Caspase 3, Caspases, Cell Survival, Densitometry, Female, Femur, Hematopoietic Stem Cells, Insulin, Leptin, Mice, Mice, Inbred C57BL, Mice, Obese, Microscopy, Confocal, Osteogenesis, Tibia, Time Factors
Applications	Beadlyte® assay
Related Products	RENDO-85K
Pub Med ID	15883640

Normal mice and leptin-deficient ob/ob mice were treated with leptin to study effects on osteogenesis and adipogenesis in bone marrow. Leptin treatment significantly decreased bone marrow adipocyte size and number in ob/ob mice while increasing bone formation, BMC, and BMD. The results suggest that, in leptin-sensitive animals, the reduction in marrow adipocytes has positive effects on bone formation. INTRODUCTION: Adipocytes, osteoblasts, and osteoclasts have leptin receptors, and leptin can also affect bone metabolism indirectly through its receptors in the hypothalamus. We examined the effects of leptin treatment on bone formation, BMD, and marrow adipocyte population in normal mice and leptin-deficient ob/ob mice. MATERIALS AND METHODS: At the age of 15 weeks, mice were implanted with Alzet osmotic pumps for subcutaneous delivery of treatment solutions (saline, 2.5 microg leptin/day, or 10 microg leptin/day) for 14 days at a delivery rate of 0.25 microl/h. Bone formation was assessed using fluorochrome labels, cell populations were quantified using histomorphometry, and bone densitometry was measured using DXA. We also used a Luminex Beadlyte assay system to quantify cell survival markers in bone marrow samples. RESULTS AND CONCLUSIONS: Results indicate that both doses of leptin decreased the number of marrow adipocytes in ob/ob mice by >20% (p 0.05) compared with PBS-treated ob/ob mice. The decrease in adipocyte number with leptin treatment is accompanied by an increase in concentration of the apoptosis marker caspase-3 in bone marrow adipocytes and hematopoietic cells. Both leptin doses also significantly (p 0.05) increased the percentage of fluorochrome-labeled tibial endosteal surface by >30% compared with PBS-treated ob/ob mice. Leptin treatment increased whole body BMC by >30% in the ob/ob mice receiving the highest leptin dose. Leptin treatment provided no increase in bone formation, BMC, or BMD in normal, leptin-replete mice.