Carroll K A, Sawden M, Sharma S
Department of Immunology, Tufts University, Boston, MA, 02111, USA.
Graduate School of Biomedical Sciences, Tufts University, Boston, MA, 02111, USA.
Curr Osteoporos Rep. 2025 Jan 14;23(1):6. doi: 10.1007/s11914-024-00900-3.
The purpose of this review is to summarize the current understanding of cell-autonomous innate immune pathways that contribute to bone homeostasis and disease.
Germ-line encoded pattern recognition receptors (PRRs) are the first line of defense against danger and infections. In the bone microenvironment, PRRs and downstream signaling pathways, that mount immune defense, interface intimately with the core cellular processes in bone cells to alter bone formation and resorption. The role of PRR engagement on bone remodeling has been best described as a result of activated macrophages secreting effector molecules that reshape the characteristics of bone-resident cells. However, it is being increasingly recognized that local bone resident-cells like osteoclasts and osteoblasts possess an arsenal of PRRs. The engagement of these PRRs by stimuli in the bone niche can drive cell-autonomous (aka cell-intrinsic) responses that, in turn, impact bone-remodeling dramatically, irrespective of immune cell effectors. Indeed, this vital role for cell-autonomous innate immune responses is evident in how reduced PRR activity within osteoclast progenitors correlates with their reduced differentiation and abnormal bone remodeling. Further, cell-intrinsic PRR activity has now been shown to influence the behavior of osteoblasts, osteocytes and other local immune/non-immune cell populations. However, distinct PRR families have varying impact on bone homeostasis and inflammation, emphasizing the importance of investigating these different nodes of innate immune signaling in bone cells to better identify how they synergistically and/or antagonistically regulate bone remodeling in the course of an immune response. Innate immune sensing within bone resident cells is a critical determinant for bone remodeling in health and disease.
本综述旨在总结目前对有助于骨稳态和疾病的细胞自主性固有免疫途径的理解。
种系编码的模式识别受体（PRR）是抵御危险和感染的第一道防线。在骨微环境中，引发免疫防御的PRR及其下游信号通路与骨细胞的核心细胞过程密切相关，以改变骨形成和骨吸收。PRR参与对骨重塑的作用，最好的描述是活化的巨噬细胞分泌效应分子，从而重塑骨驻留细胞的特性。然而，人们越来越认识到，破骨细胞和成骨细胞等局部骨驻留细胞拥有一系列PRR。骨微环境中的刺激物与这些PRR的结合可驱动细胞自主性（即细胞内在性）反应，进而显著影响骨重塑，而与免疫细胞效应器无关。事实上，破骨细胞前体细胞内PRR活性降低与其分化减少和异常骨重塑之间的关联，明显体现了细胞自主性固有免疫反应的这一重要作用。此外，现已表明细胞内在性PRR活性会影响成骨细胞、骨细胞和其他局部免疫/非免疫细胞群体的行为。然而，不同的PRR家族对骨稳态和炎症的影响各不相同，这强调了研究骨细胞中这些不同的固有免疫信号节点的重要性，以便更好地确定它们在免疫反应过程中如何协同和/或拮抗调节骨重塑。骨驻留细胞内的固有免疫感应是健康和疾病状态下骨重塑的关键决定因素。
