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

被引:205
作者
Hamrick, MW
Della-Fera, MA
Choi, YH
Pennington, C
Baile, CA
机构
[1] Med Coll Georgia, Dept Cellular Biol & Anat, Augusta, GA 30912 USA
[2] Univ Georgia, Athens, GA 30602 USA
关键词
adipogenesis; apoptosis; osteogenesis; bone mass; BMD;
D O I
10.1359/JBMR.050103
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 mu g leptin/day, or 10 mu g leptin/day) for 14 days at a delivery rate of 0.25 mu l/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.
引用
收藏
页码:994 / 1001
页数:8
相关论文
共 48 条
  • [1] Amling M, 2000, BIOESSAYS, V22, P970
  • [2] Regulation of metabolism and body fat mass by leptin
    Baile, CA
    Della-Fera, MA
    Martin, RJ
    [J]. ANNUAL REVIEW OF NUTRITION, 2000, 20 : 105 - 127
  • [3] Effects of dietary restriction on total body, femoral, and vertebral bone in SENCAR, C57BL/6, and DBA/2 mice
    Brochmann, EJ
    Duarte, ME
    Zaidi, HA
    Murray, SS
    [J]. METABOLISM-CLINICAL AND EXPERIMENTAL, 2003, 52 (10): : 1265 - 1273
  • [4] Leptin reduces ovariectomy-induced bone loss in rats
    Burguera, B
    Hofbauer, LC
    Thomas, T
    Gori, F
    Evans, GL
    Khosla, S
    Riggs, BL
    Turner, RT
    [J]. ENDOCRINOLOGY, 2001, 142 (08) : 3546 - 3553
  • [5] Effects of increased muscle mass on mouse sagittal suture morphology and mechanics
    Byron, CD
    Borke, J
    Yu, J
    Pashley, D
    Wingard, CJ
    Hamrick, M
    [J]. ANATOMICAL RECORD PART A-DISCOVERIES IN MOLECULAR CELLULAR AND EVOLUTIONARY BIOLOGY, 2004, 279A (01): : 676 - 684
  • [6] The phosphoinositide 3-kinase pathway
    Cantley, LC
    [J]. SCIENCE, 2002, 296 (5573) : 1655 - 1657
  • [7] Leptin directly regulates bone cell function in vitro and reduces bone fragility in vivo
    Cornish, J
    Callon, KE
    Bava, U
    Lin, C
    Naot, D
    Hill, BL
    Grey, AB
    Broom, N
    Myers, DE
    Nicholson, GC
    Reid, IR
    [J]. JOURNAL OF ENDOCRINOLOGY, 2002, 175 (02) : 405 - 415
  • [8] Resistance to IP leptin-induced adipose apoptosis caused by high-fat diet in mice
    Della-Fera, MA
    Li, CL
    Baile, CA
    [J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2003, 303 (04) : 1053 - 1057
  • [9] Adipocyte apoptosis in the regulation of body fat mass by leptin
    Della-Fera, MA
    Qian, H
    Baile, CA
    [J]. DIABETES OBESITY & METABOLISM, 2001, 3 (05) : 299 - 310
  • [10] Fat body mass, leptin and femur bone mineral density in hip-fractured women
    Di Monaco, M
    Vallero, F
    Di Monaco, R
    Mautino, F
    Cavanna, A
    [J]. JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION, 2003, 26 (12) : 1180 - 1185