Replacement of bone marrow by bone in rat femurs: the bone bioreactor.
Replacement of bone marrow by bone in rat femurs: the bone bioreactor.
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DOI：
10.1089/tea.2007.0261
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发表时间：
2008-02
影响因子：
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通讯作者：
Qing Zhang;Esteban Cuartas;N. Mehta;J. Gilligan;H. Ke;W. Mark Saltzman;M. Kotas;Mandy Ma;Sonali Rajan;Cecile Chalouni;J. Carlson;A. Vignery
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作者：
Qing Zhang;Esteban Cuartas;N. Mehta;J. Gilligan;H. Ke;W. Mark Saltzman;M. Kotas;Mandy Ma;Sonali Rajan;Cecile Chalouni;J. Carlson;A. Vignery
在骨的发育和修复过程中，膜内和软骨内两种不同但互补的机制通过成骨细胞介导新骨形成。由于机械骨髓消融导致骨髓腔中新骨的快速和短暂形成，因此我们假设甲状旁腺激素（PTH）是一种骨合成代谢激素，可增强骨髓消融后形成的新骨的形成。我们对大鼠的左股骨进行机械骨髓消融或假手术，并在第一个实验中每天注射PTH或溶媒，持续1、2或3周，然后在第二个实验中注射PTH、甲状旁腺相关肽（PTHrP）或溶媒，持续3周。我们从每只大鼠的股骨进行软X射线，外周定量计算机断层扫描，计算机断层扫描的微型，和组织学分析，并确定血清骨钙素的浓度。此外，在第二个实验中，我们测定了3周时血清钙、抗酒石酸酸性磷酸酶（TRAP）和NF-κ B配体受体激活剂（RANKL）的浓度，并对股骨进行生物力学测试。在用PTH或PTHrP治疗3周后，骨填充了其骨髓已被消融的干的骨髓腔。PTH增加右侧股骨的骨小梁密度，但未能诱导右侧未手术股骨干髓区的骨形成。与对照组、假手术组和溶剂处理组大鼠的右股骨和左股骨相比，新形成的骨赋予左股骨干改善的生物力学性能。PTHrP，像PTH，增加血清骨钙素，但既不增加血清钙，TRAP，或RANKL在3周。我们的研究结果表明，骨髓切除后新形成的骨骼对甲状旁腺激素有反应，扩大了甲状旁腺激素在骨骼中的作用，并可能为再生医学和组织工程领域的研究开辟新的途径。局部骨髓清除结合合成代谢药物干预可能提供一种在高骨丢失区域快速优先定向骨生长的技术。
During development and repair of bone, two distinct yet complementary mechanisms, intramembranous and endochondral, mediate new bone formation via osteoblasts. Because mechanical bone marrow ablation leads to the rapid and transient formation of new bone in the marrow cavity, we postulated that parathyroid hormone (PTH), which is a bone anabolic hormone, enhances the formation of new bone that forms after marrow ablation. We subjected the left femur of rats to mechanical marrow ablation, or sham operation, and injected the animals daily with PTH or vehicle for 1, 2, or 3 weeks in a first experiment, then with PTH, parathyroid hormone-related peptide (PTHrP), or vehicle for 3 weeks in a second experiment. We subjected both femurs from each rat to soft X-ray, peripheral quantitative computed tomography, computed tomography on a microscale, and histological analysis, and determined the concentration of serum osteocalcin. In addition, in the second experiment, we determined the serum concentration of calcium, tartrate-resistant acid phosphatase (TRAP), and receptor activator of NF-kappaB ligand (RANKL) at 3 weeks, and subjected femurs to biomechanical testing. Following treatment with PTH or PTHrP for 3 weeks, bone filled the marrow cavity of the shafts whose marrow had been ablated. PTH increased trabecular density in the right femur, but failed to induce bone formation in the medullary region of the right unoperated femoral shafts. The newly formed bone endowed left femoral shafts with improved biomechanical properties when compared to those of right femurs and left femurs from control, sham-operated, and vehicle-treated rats. PTHrP, like PTH, increased serum osteocalcin, but neither increased serum calcium, TRAP, or RANKL at 3 weeks. Our results reveal that the newly formed bone that follows marrow ablation is responsive to PTH, expand the role of PTH in bone, and might open new avenues of investigations to the field of regenerative medicine and tissue engineering. Local bone marrow removal in conjunction with pharmacologic intervention with an anabolic agent might provide a technique for rapid preferential site-directed bone growth in areas of high bone loss.