Advanced imaging to understand bone's adaptation to mechanical load

先进的成像技术可了解骨骼对机械负荷的适应

• 批准号: RGPIN-2018-03908
• 负责人: Manske, Sarah
• 金额: $ 1.75万
• 依托单位: University of Calgary
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=764460
• 关键词: Advanced; imaging; understand; bone; adaptation

Bone is a dynamic tissue that changes in response to its environment by adding or removing bone depending on the signals it receives. These signals can include mechanical (e.g., loading through exercise) and inflammation (e.g., swelling from an injury). Although bone's response to exercise and other forms of loading have been studied, how bone changes in complex environments with changing mechanical and inflammatory signals is not well understood. Advances in imaging techniques such as computed tomography (CT) and magnetic resonance imaging (MRI) mean that we are now able to study bone and the tissues around bone in living people and animals at the same time, and can better capture changes in bone over time. This means that we can develop a better understanding of how and why bone changes in response to activities such as exercise or bedrest, and how bone interacts with tissues surrounding it. The long-term goal of my research program is to develop and apply advanced imaging techniques to better understand the mechanism by which bone adapts to mechanical signals. The proposed work will use novel imaging techniques using micro-computed tomography (micro-CT, ideal for bone imaging), MRI (ideal for soft tissue imaging) and 3D image registration to test new hypotheses regarding the interaction between mechanical loading and inflammation on quantitative measures of bone adaptation. Over the course of this five year grant, my objective is to apply 3D image registration techniques to quantify bone formation and resorption at sites of interaction between bone and soft tissue to evaluate changes in bone volume and microarchitecture over time. I will examine bone adaptation in two animal models at two points of bone-soft tissue interaction: 1) muscle attachment sites in a well-established muscle disuse model in mice, and 2) bony spur, or osteophyte, formation at the edges of joints in guinea pigs to test the hypothesis that bone's local response to mechanical stimuli is tightly mediated by mechanical interaction with soft tissues such as muscle, ligament and cartilage, while the more distant response is controlled primarily by inflammatory pathways. In the mouse model, I will manipulate mechanical loading by inducing muscle disuse via botulinum toxin injection, while in the guinea pig I will manipulate mechanical loading by altering joint stability via anterior cruciate ligament transection. I will perturb the inflammatory environment using anti-inflammatory drugs. The proposed work will enhance our ability to measure bone changes in living animals, and determine whether inflammation dominates bone loss close to and far from muscle attachment sites as well as bone spur formation after joint injury. The findings from the proposed research program will improve understanding of the stimuli that drive bone formation and resorption, and will have substantial implications for enhancing bone formation in humans.

骨是一种动态组织，其通过根据其接收的信号添加或移除骨来响应其环境而变化。这些信号可以包括机械（例如，通过运动的负荷）和炎症（例如，因受伤而肿胀）。虽然已经研究了骨骼对运动和其他形式的负荷的反应，但骨骼在复杂环境中如何随着机械和炎症信号的变化而变化还没有很好的理解。计算机断层扫描（CT）和磁共振成像（MRI）等成像技术的进步意味着我们现在能够同时研究活人和动物的骨骼和骨骼周围的组织，并且可以更好地捕捉骨骼随时间的变化。这意味着我们可以更好地了解骨骼如何以及为什么会在运动或卧床休息等活动中发生变化，以及骨骼如何与周围组织相互作用。我的研究计划的长期目标是开发和应用先进的成像技术，以更好地了解骨骼适应机械信号的机制。拟议的工作将使用新的成像技术，使用微计算机断层扫描（微CT，理想的骨成像），MRI（理想的软组织成像）和3D图像配准，以测试关于机械负荷和炎症之间的相互作用的新假设对骨适应的定量测量。在这个为期五年的资助过程中，我的目标是应用3D图像配准技术来量化骨和软组织之间相互作用部位的骨形成和吸收，以评估骨体积和微结构随时间的变化。我将在两个动物模型中检查骨-软组织相互作用的两个点的骨适应性：1）在小鼠中建立良好的肌肉废用模型中的肌肉附着位点，和2）在豚鼠中关节边缘处的骨刺或骨赘形成，以测试骨对机械刺激的局部响应由与软组织（例如肌肉）的机械相互作用紧密介导的假设，韧带和软骨，而更远的反应主要由炎症途径控制。在小鼠模型中，我将通过注射肉毒杆菌毒素诱导肌肉废用来操纵机械负荷，而在豚鼠模型中，我将通过切断前交叉韧带来改变关节稳定性来操纵机械负荷。我会用消炎药扰乱炎症环境。拟议的工作将提高我们测量活体动物骨骼变化的能力，并确定炎症是否主导了靠近和远离肌肉附着部位的骨丢失以及关节损伤后的骨刺形成。拟议研究计划的发现将提高对驱动骨形成和吸收的刺激的理解，并将对增强人类骨形成产生重大影响。