Hamrick Mark W, Della Fera Mary Anne, Choi Yang-Ho, Hartzell Diane, Pennington Catherine, Baile Clifton A
Department of Cellular Biology and Anatomy, Medical College of Georgia, Laney Walker Blvd. CB2915, Augusta, GA 30912, USA.
Cell Tissue Res. 2007 Jan;327(1):133-41. doi: 10.1007/s00441-006-0312-3. Epub 2006 Sep 22.
The accumulation of fat cells (adipocytes) in bone marrow is now thought to be a factor contributing to age-related bone loss. Women with osteoporosis have higher numbers of marrow adipocytes than women with healthy bone, and bone formation rate is inversely correlated with adipocyte number in bone tissue biopsies from both men and women. Adipogenic differentiation of bone marrow stromal cells increases with age, but the factors regulating populations of mature adipocytes are not well understood. Leptin is thought to regulate adipose tissue mass via its receptors in the ventromedial hypothalamus (VMH). We have therefore tested the hypothesis that stimulation of leptin receptors in the VMH regulates adipocyte number in bone marrow. Results indicate that unilateral twice-daily injections of leptin into the rat VMH for only 4 or 5 days cause a significant reduction in the number of adipocytes in peripheral fat pads and bone marrow and indeed eliminate adipocytes almost entirely from bone marrow of the proximal tibia. Osteoblast surface is not affected with leptin treatment. Apoptosis assays performed on bone marrow samples from control and treated rats have revealed a significant increase in protein concentration of the apoptosis marker caspase-3 with leptin treatment. We conclude that stimulation of leptin receptors in the VMH significantly decreases the adipocyte population in bone marrow, primarily through apoptosis of marrow adipocytes. Elimination of marrow adipocytes via this central pathway may represent a useful strategy for the treatment and prevention of osteoporosis.
现在认为骨髓中脂肪细胞（脂肪细胞）的积累是导致与年龄相关的骨质流失的一个因素。患有骨质疏松症的女性比骨骼健康的女性有更多的骨髓脂肪细胞，并且在男性和女性的骨组织活检中，骨形成率与脂肪细胞数量呈负相关。骨髓基质细胞的脂肪生成分化随年龄增加，但调节成熟脂肪细胞数量的因素尚不清楚。瘦素被认为通过其在下丘脑腹内侧核（VMH）中的受体调节脂肪组织量。因此，我们测试了以下假设：刺激VMH中的瘦素受体会调节骨髓中的脂肪细胞数量。结果表明，仅在4或5天内每天两次向大鼠VMH单侧注射瘦素，会导致外周脂肪垫和骨髓中脂肪细胞数量显著减少，实际上几乎完全消除了胫骨近端骨髓中的脂肪细胞。瘦素处理对成骨细胞表面没有影响。对对照大鼠和处理大鼠的骨髓样本进行的凋亡分析显示，瘦素处理后凋亡标志物半胱天冬酶-3的蛋白浓度显著增加。我们得出结论，刺激VMH中的瘦素受体会显著减少骨髓中的脂肪细胞数量，主要是通过骨髓脂肪细胞的凋亡。通过这一中心途径消除骨髓脂肪细胞可能是治疗和预防骨质疏松症的一种有用策略。
