Josephson Timothy O, Morgan Elise F
Biomedical Engineering, Boston University, Boston, MA, United States.
Center for Multiscale and Translational Mechanobiology, Boston University, Boston, MA, United States.
Front Physiol. 2023 Oct 9;14:1232698. doi: 10.3389/fphys.2023.1232698. eCollection 2023.
At the macroscale, bones experience a variety of compressive and tensile loads, and these loads cause deformations of the cortical and trabecular microstructure. These deformations produce a variety of stimuli in the cellular microenvironment that can influence the differentiation of marrow stromal cells (MSCs) and the activity of cells of the MSC lineage, including osteoblasts, osteocytes, and chondrocytes. Mechanotransduction, or conversion of mechanical stimuli to biochemical and biological signals, is thus part of a multiscale mechanobiological process that drives bone modeling, remodeling, fracture healing, and implant osseointegration. Despite strong evidence of the influence of a variety of mechanical cues, and multiple paradigms proposed to explain the influence of these cues on tissue growth and differentiation, even a working understanding of how skeletal cells respond to the complex combinations of stimuli in their microenvironments remains elusive. This review covers the current understanding of what types of microenvironmental mechanical cues MSCs respond to and what is known about how they respond in the presence of multiple such cues. We argue that in order to realize the vast potential for harnessing the cellular microenvironment for the enhancement of bone regeneration, additional investigations of how combinations of mechanical cues influence bone regeneration are needed.
在宏观层面，骨骼承受各种压缩和拉伸负荷，这些负荷会导致皮质和小梁微观结构发生变形。这些变形会在细胞微环境中产生各种刺激，从而影响骨髓间充质干细胞（MSC）的分化以及MSC谱系细胞（包括成骨细胞、骨细胞和软骨细胞）的活性。因此，机械转导，即将机械刺激转化为生化和生物信号，是驱动骨建模、重塑、骨折愈合和植入物骨整合的多尺度机械生物学过程的一部分。尽管有充分证据表明各种机械信号具有影响，并且提出了多种范式来解释这些信号对组织生长和分化的影响，但即使是对骨骼细胞如何响应其微环境中复杂刺激组合的基本理解仍然难以捉摸。本综述涵盖了目前对MSCs对何种类型的微环境机械信号作出反应以及在存在多种此类信号时它们如何作出反应的理解。我们认为，为了实现利用细胞微环境促进骨再生的巨大潜力，需要进一步研究机械信号组合如何影响骨再生。
