Disparate osteogenic response of mandible and iliac crest bone marrow stromal cells to pamidronate.

Disparate osteogenic response of mandible and iliac crest bone marrow stromal cells to pamidronate.
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DOI:
10.1111/j.1601-0825.2007.01402.x
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发表时间:
2008-07
期刊:
影响因子:
3.8
通讯作者:
Akintoye SO
Akintoye SO
中科院分区:
医学3区
文献类型:
--
作者:
Stefanik D;Sarin J;Lam T;Levin L;Leboy PS;Akintoye SO

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长期静脉注射双磷酸盐(如帕米膦酸)与颌骨坏死有关,但中轴骨和四肢骨不受影响。双膦酸盐相关颌骨坏死的发病机制可能与双膦酸盐对口面部和中轴/四肢骨的骨髓基质细胞(BMSC)成骨分化的骨骼位点特异性影响有关。本研究评估并比较了下颌骨(口面骨)和髂嵴(轴骨)人 BMSC 对帕米膦酸盐的骨骼位点特异性成骨反应。取自 6 名正常健康志愿者的下颌骨和髂嵴 BMSC 进行培养,并用帕米磷酸盐进行测试,以评估和比较细胞存活、成骨标志物碱性磷酸酶、与 CD34+ 造血干细胞共培养中的破骨细胞分化、NFκB 配体受体激活剂 (RANKL) 和骨保护素的基因表达以及体内骨再生。下颌骨 BMSC 比髂嵴 BMSC 更容易受到帕米膦酸的影响,因为细胞存活率降低、碱性磷酸酶产量降低以及体内骨再生结构组织较差。帕米膦酸钠促进下颌骨 BMSC 更高的 RANKL 基因表达和破骨细胞募集。帕米膦酸钠对下颌骨和髂嵴 BMSC 的存活和成骨分化有不同的影响,有利于下颌骨稳态失调。
Long-term administration of intravenous bisphosphonates like pamidronate is associated with jaw osteonecrosis but axial and appendicular bones are unaffected. Pathogenesis of bisphosphonate-associated jaw osteonecrosis may relate to skeletal-site specific effects of bisphosphonates on osteogenic differentiation of bone marrow stromal cells (BMSCs) of orofacial and axial/appendicular bones. This study evaluated and compared skeletal site-specific osteogenic response of mandible (orofacial bone) and iliac crest (axial bone) human BMSCs to pamidronate. Mandible and iliac crest BMSCs from six normal healthy volunteers were established in culture and tested with pamidronate to evaluate and compare cell survival, osteogenic marker alkaline phosphatase, osteoclast differentiation in co-cultures with CD34+ hematopoietic stem cells, gene expression of receptor activator of NFκB ligand (RANKL) and osteoprotegerin, and in vivo bone regeneration. Mandible BMSCs were more susceptible to pamidronate than iliac crest BMSCs based on decreased cell survival, lower alkaline phosphatase production and structurally less organized in vivo bone regeneration. Pamidronate promoted higher RANKL gene expression and osteoclast recruitment by mandible BMSCs. Mandible and iliac crest BMSC survival and osteogenic differentiation are disparately affected by pamidronate to favor dysregulated mandible bone homeostasis.
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