Rodriguez-Feo John, Fernandes Lorenzo, Patel Anuj, Doan Thanh, Boden Scott D, Drissi Hicham, Presciutti Steven M
Department of Orthopaedic Surgery Emory University Atlanta Georgia USA.
Atlanta Veteran Affairs Medical Center Decatur Georgia USA.
JOR Spine. 2020 Jun 25;4(1):e1100. doi: 10.1002/jsp2.1100. eCollection 2021 Mar.
The bone healing environment in the posterolateral spine following arthrodesis surgery is one of the most challenging in all of orthopedics and our understanding of the molecular signaling pathways mediating osteogenesis during spinal fusion is limited. In this study, the spatial and temporal expression pattern of Wnt signaling factors and inhibitors during spinal fusion was assessed for the first time. Bilateral posterolateral spine arthrodesis with autologous iliac crest bone graft was performed on 21 New Zealand White rabbits. At 1-, 2-, 3-, 4-, and 6-weeks, the expression of sclerostin and a variety of canonical and noncanonical Wnts signaling factors was measured by qRT-PCR from tissue separately collected from the transverse processes, the Outer and Inner Zones of the fusion mass, and the adjancent paraspinal muscle. Immunohistochemistry for sclerostin protein was also performed. Sclerostin and many Wnt factors, especially Wnt3a and Wnt5a, were found to have distinct spatial and temporal expression patterns. For example, harvesting ICBG caused a significant increase in sclerostin expression. Furthermore, the paraspinal muscle immediately adjacent to the transplanted ICBG also had significant increases in sclerostin expression at 3 weeks, suggesting new potential mechanisms for pseudarthroses following spinal arthrodesis. The presented work is the first description of the spatial and temporal expression of sclerostin and Wnt signaling factors in the developing spine fusion, filling an important knowledge gap in the basic biology of spinal fusion and potentially aiding in the development of novel biologics to increase spinal fusion rates.
后路脊柱融合手术后，后外侧脊柱的骨愈合环境是所有骨科领域中最具挑战性的环境之一，而我们对脊柱融合过程中介导成骨的分子信号通路的了解有限。在本研究中，首次评估了脊柱融合过程中Wnt信号因子和抑制剂的时空表达模式。对21只新西兰白兔进行双侧后外侧脊柱融合术并植入自体髂嵴骨移植。在第1、2、3、4和6周时，通过qRT-PCR分别从横突、融合块的外层和内层区域以及相邻的椎旁肌单独收集的组织中测量硬化蛋白和多种经典及非经典Wnt信号因子的表达。还进行了硬化蛋白的免疫组织化学检测。发现硬化蛋白和许多Wnt因子，特别是Wnt3a和Wnt5a，具有不同的时空表达模式。例如，采集髂嵴骨移植组织会导致硬化蛋白表达显著增加。此外，紧邻移植髂嵴骨移植组织的椎旁肌在第3周时硬化蛋白表达也显著增加，这提示了脊柱融合术后假关节形成的新潜在机制。本研究首次描述了发育中的脊柱融合中硬化蛋白和Wnt信号因子的时空表达，填补了脊柱融合基础生物学中的一个重要知识空白，并可能有助于开发新型生物制剂以提高脊柱融合率。
