Hodgkinson Tom, Amado Isabel N, O'Brien Fergal J, Kennedy Oran D
Department of Anatomy and Regenerative Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland.
APL Bioeng. 2022 Jan 5;6(1):011501. doi: 10.1063/5.0068277. eCollection 2022 Mar.
Multifaceted changes in the mechanobiological environment of skeletal joints, at multiple length scales, are central to the development of diseases-like osteoarthritis (OA). Recent evidence demonstrates related mechanical alterations in both bone and cartilage tissues, with crosstalk between the tissues being an important factor in acute and chronic degenerative processes. However, recapitulating multicellular tissue systems in the laboratory to study the entire osteochondral unit remains challenging. Thus, the development of accurate and reproducible OA model systems and the selection of the most suitable model for individual experimental approaches are critical. This review first discusses recent progress in understanding mechanosensory processes in healthy and osteoarthritic joints. Subsequently, we review advancements in the development of and model systems ranging from 2D monocultures through to joint organ-on-a-chip models. Use of these systems allows for the study of multiple cell types in controlled, reproducible, and dynamic environments, which can incorporate precisely controlled mechanical and biochemical stimuli, and biophysical cues. The way in which these models have, and will continue to, improve our ability to recapitulate complex mechanical/paracrine signaling pathways in osteochondral tissues is then discussed. As the accuracy of model systems advances, they will have a significant impact on both our understanding of the pathobiology of OA and in identifying and screening therapeutic targets to improve treatment of this complex disease.
在多个长度尺度上，骨骼关节的机械生物学环境发生多方面变化，这是骨关节炎（OA）等疾病发展的核心。最近的证据表明，骨骼和软骨组织中都存在相关的力学改变，组织间的相互作用是急性和慢性退变过程中的一个重要因素。然而，在实验室中重现多细胞组织系统以研究整个骨软骨单元仍然具有挑战性。因此，开发准确且可重复的OA模型系统以及为个别实验方法选择最合适的模型至关重要。本综述首先讨论了在理解健康和骨关节炎关节的机械感觉过程方面的最新进展。随后，我们回顾了从二维单培养到关节芯片模型等模型系统的发展进步。使用这些系统可以在可控、可重复和动态的环境中研究多种细胞类型，这些环境可以纳入精确控制的机械和生化刺激以及生物物理线索。然后讨论了这些模型已经以及将继续如何提高我们在骨软骨组织中重现复杂机械/旁分泌信号通路的能力。随着模型系统准确性的提高，它们将对我们对OA病理生物学的理解以及识别和筛选治疗靶点以改善这种复杂疾病的治疗产生重大影响。
