Ciliary Neurotrophic Factor Inhibits Bone Formation and Plays a Sex-Specific Role in Bone Growth and Remodeling
Ciliary Neurotrophic Factor Inhibits Bone Formation and Plays a Sex-Specific Role in Bone Growth and Remodeling
复制标题
睫状神经营养因子抑制骨形成并在骨生长和重塑过程中发挥性别特异性作用
DOI：
10.1007/s00223-010-9337-4
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发表时间：
2010-03-01
影响因子：
4.2
通讯作者：
Sims, Natalie A.
中科院分区：
文献类型：
--
作者：
McGregor, Narelle E.;Poulton, Ingrid J.;Sims, Natalie A.
已描述成骨样细胞中睫状神经营养因子（CNTF）受体（CNTFR）的表达，表明CNTF在骨代谢中发挥作用。当与CNTF、神经生成素（NP）或心肌营养素样细胞因子（CLC）结合时，CNTFR与gp 130和白血病抑制因子受体形成信号复合物，这两者在骨细胞生物学中起关键作用。本研究旨在确定CNTFR信号细胞因子在骨中的作用。免疫组化检测CNTF在成骨细胞、骨细胞、破骨细胞和增殖软骨细胞中的表达。CNTFR mRNA在原代颅骨成骨细胞中检测到，并在成骨细胞分化过程中上调。用CNTF或CLC处理成骨细胞，而不是NP，显着抑制矿化和osterix mRNA水平。15周龄雄性CNTF（-/-）小鼠表现出股骨长度、皮质厚度和骨膜周长减少;但股骨骨小梁骨矿物质密度（Tb.BMD）和胫骨骨小梁骨体积（BV/TV）与野生型无显著差异，表明CNTF在雄性小鼠骨生长中的独特作用。女性CNTF（-/-）股骨宽度正常，但股骨Tb、BMD、胫骨BV/TV、骨小梁数量和骨小梁厚度均增加。与野生型同窝仔相比，雌性CNTF（-/-）小鼠也表现出较高的成骨细胞数量和矿物质沉积率，这是成骨细胞谱系固有的。CNTF在骨中局部表达，在雌性小鼠中作为骨小梁形成的抑制剂和在雄性小鼠中作为皮质生长的刺激剂发挥独特作用。
Ciliary neurotrophic factor (CNTF) receptor (CNTFR) expression has been described in osteoblast-like cells, suggesting a role for CNTF in bone metabolism. When bound to CNTF, neuropoietin (NP), or cardiotrophin-like-cytokine (CLC), CNTFR forms a signaling complex with gp130 and the leukemia inhibitory factor receptor, which both play critical roles in bone cell biology. This study aimed to determine the role of CNTFR-signaling cytokines in bone. Immunohistochemistry detected CNTF in osteoblasts, osteocytes, osteoclasts, and proliferating chondrocytes. CNTFR mRNA was detected in primary calvarial osteoblasts and was upregulated during osteoblast differentiation. Treatment of osteoblasts with CNTF or CLC, but not NP, significantly inhibited mineralization and osterix mRNA levels. Twelve-week-old male CNTF (-/-) mice demonstrated reduced femoral length, cortical thickness, and periosteal circumference; but femoral trabecular bone mineral density (Tb.BMD) and tibial trabecular bone volume (BV/TV) were not significantly different from wild-type, indicating a unique role for CNTF in bone growth in male mice. In contrast, female CNTF (-/-) femora were of normal width, but femoral Tb.BMD, tibial BV/TV, trabecular number, and trabecular thickness were all increased. Female CNTF (-/-) tibiae also demonstrated high osteoblast number and mineral apposition rate compared to wild-type littermates, and this was intrinsic to the osteoblast lineage. CNTF is expressed locally in bone and plays a unique role in female mice as an inhibitor of trabecular bone formation and in male mice as a stimulus of cortical growth.