Department of Molecular Bone Biology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Department of Cell Biology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Front Endocrinol (Lausanne). 2023 May 9;14:1181204. doi: 10.3389/fendo.2023.1181204. eCollection 2023.
Bone contributes to the maintenance of vital biological activities. At the cellular level, multiple types of skeletal cells, including skeletal stem and progenitor cells (SSPCs), osteoblasts, chondrocytes, marrow stromal cells, and adipocytes, orchestrate skeletal events such as development, aging, regeneration, and tumorigenesis. Osteosarcoma (OS) is a primary malignant tumor and the main form of bone cancer. Although it has been proposed that the cellular origins of OS are in osteogenesis-related skeletal lineage cells with cancer suppressor gene mutations, its origins have not yet been fully elucidated because of a poor understanding of whole skeletal cell diversity and dynamics. Over the past decade, the advent and development of single-cell RNA sequencing analyses and mouse lineage-tracing approaches have revealed the diversity of skeletal stem and its lineage cells. Skeletal stem cells (SSCs) in the bone marrow endoskeletal region have now been found to efficiently generate OS and to be robust cells of origin under deletion conditions. The identification of SSCs may lead to a more limited redefinition of bone marrow mesenchymal stem/stromal cells (BM-MSCs), and this population has been thought to contain cells from which OS originates. In this mini-review, we discuss the cellular diversity and dynamics of multiple skeletal cell types and the origin of OS in the native environment in mice. We also discuss future challenges in the study of skeletal cells and OS.
骨骼有助于维持重要的生物活性。在细胞水平上，多种类型的骨骼细胞，包括骨骼干细胞和祖细胞（SSPCs）、成骨细胞、软骨细胞、骨髓基质细胞和脂肪细胞，协调骨骼发育、衰老、再生和肿瘤发生等骨骼事件。骨肉瘤（OS）是一种原发性恶性肿瘤，也是骨癌的主要形式。尽管已经提出 OS 的细胞起源是具有抑癌基因突变的成骨相关骨骼谱系细胞，但由于对整个骨骼细胞多样性和动力学的了解不足，其起源尚未完全阐明。在过去的十年中，单细胞 RNA 测序分析和小鼠谱系追踪方法的出现和发展揭示了骨骼干细胞及其谱系细胞的多样性。现在已经发现骨髓内膜骨骼区域的骨骼干细胞（SSC）能够有效地产生 OS，并在删除条件下成为起源的健壮细胞。SSC 的鉴定可能会导致对骨髓间充质干细胞（BM-MSCs）的更有限的重新定义，并且该群体被认为包含起源于 OS 的细胞。在这篇迷你综述中，我们讨论了多种骨骼细胞类型的细胞多样性和动力学以及 OS 在小鼠天然环境中的起源。我们还讨论了骨骼细胞和 OS 研究中的未来挑战。
