Intercellular Interactions of an Adipogenic CXCL12-Expressing Stromal Cell Subset in Murine Bone Marrow

Chu, Angel Ka Yan; Ono, Wanida; Welch, Joshua D.; Ono, Noriaki

doi:10.1002/jbmr.4282

Cited by 16 publications

(19 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The emerging concept is that a subset of bone marrow stromal cells termed CXCL12-abundant reticular stromal cells (CAR cells) are composed of two distinct cellular subsets of pre-osteoblast-like (Osteo-CAR) cells and pre-adipocyte-like (Adipo-CAR) cells 37 . Our recent study demonstrates that Osteo-CAR and Adipo-CAR cells are likely to represent independent cell lineages that do not contribute one another 39 . Our findings provide preliminary evidence that quiescent pre-adipocyte-like marrow stromal (Adipo-CAR) cells in the diaphyseal marrow space might preferentially originate from the fetal perichondrium, while more active pre-osteoblast-like marrow stromal (Osteo-CAR) cells in the metaphyseal marrow space might predominantly originate from the fetal cartilage during bone marrow development.…”

Section: Discussionmentioning

confidence: 97%

The fate of early perichondrial cells in developing bones

et al. 2022

Self Cite

View full text Add to dashboard Cite

In endochondral bone development, bone-forming osteoblasts and bone marrow stromal cells have dual origins in the fetal cartilage and its surrounding perichondrium. However, how early perichondrial cells distinctively contribute to developing bones remain unidentified. Here we show using in vivo cell-lineage analyses that Dlx5+ fetal perichondrial cells marked by Dlx5-creER do not generate cartilage but sustainably contribute to cortical bone and marrow stromal compartments in a manner complementary to fetal chondrocyte derivatives under the regulation of Hedgehog signaling. Postnatally, Dlx5+ fetal perichondrial cell derivatives preferentially populate the diaphyseal marrow stroma with a dormant adipocyte-biased state and are refractory to parathyroid hormone-induced bone anabolism. Therefore, early perichondrial cells of the fetal cartilage are destined to become an adipogenic subset of stromal cells in postnatal diaphyseal bone marrow, supporting the theory that the adult bone marrow stromal compartments are developmentally prescribed within the two distinct cells-of-origins of the fetal bone anlage.

show abstract

Section: Discussionmentioning

confidence: 97%

The fate of early perichondrial cells in developing bones

et al. 2022

Self Cite

View full text Add to dashboard Cite

show abstract

“…The next important question is, what are the potential cell nonautonomous mechanisms that regulate premature marrow adiposity associated with CXCL12-deficient BMSCs? More recent studies demonstrate that many CXCL12 + preadipocyte-like cells (Cxcl12-creER + , Adipo-CAR cells) are physically coupled with hematopoietic cells, particularly with B-cell precursors, monocytes and granulocytes, in a protease-sensitive manner, possibly through CXCL12-CXCR4 interactions (51). Further, CXCL12 deletion in BMSCs using Col2a1-cre leads to a reduction of stromalhematopoietic coupling and extensive marrow adipogenesis specifically in adult bone marrow (Figure 2B).…”

Section: Cxcl12-mediated Cell Non-autonomous Mechanisms Direct Bone M...mentioning

confidence: 92%

“…Importantly, CXCL12 is most abundantly expressed by reticular stromal cells in the central marrow space, and plays important roles in maintaining hematopoietic stem and progenitor cells (43)(44)(45)(46)(47)(48)(49). In fact, CXCL12 deletion in BMSCs causes reduction in hematopoietic cells in bone marrow (50,51).…”

Section: Adipogenic Subset Of Cxcl12 + Lepr + Cells (Adipo-car Cells)...mentioning

confidence: 99%

Toward Marrow Adipocytes: Adipogenic Trajectory of the Bone Marrow Stromal Cell Lineage

Ono

2022

Front. Endocrinol.

Self Cite

View full text Add to dashboard Cite

Bone marrow contains precursor cells for osteoblasts and adipocytes in the stromal compartment. Bone marrow adipose tissue (BMAT) is an important constituent of the bone marrow that is particularly abundant in adults. BMAT is composed of the proximal “regulated” BMAT containing individual adipocytes interspersed within actively hematopoietic marrow, and the distal “constitutive” BMAT containing large adipocytes in the area of low hematopoiesis. Historically, bone marrow adipocytes were regarded as one of the terminal states of skeletal stem cells, which stand at the pinnacle of the lineage and possess trilineage differentiation potential into osteoblasts, chondrocytes and adipocytes. Recent single-cell RNA-sequencing studies uncover a discrete group of preadipocyte-like cells among bone marrow stromal cells (BMSCs), and recent mouse genetic lineage-tracing studies reveal that these adipocyte precursor cells possess diverse functions in homeostasis and regeneration. These adipogenic subsets of BMSCs are abundant in the central marrow space and can directly convert not only into lipid-laden adipocytes but also into skeletal stem cell-like cells and osteoblasts under regenerative conditions. It remains determined whether there are distinct adipocyte precursor cell types contributing to two types of BMATs. In this short review, we discuss the functions of the recently identified subsets of BMSCs and their trajectory toward marrow adipocytes, which is influenced by multiple modes of cell-autonomous and non-cell autonomous regulations.

show abstract

“…Current single‐cell RNA‐seq analysis revealed the diversity of BMSCs and CAR cells (Baccin et al, 2020; Baryawno et al, 2019; Matsushita, Nagata, et al, 2020; Tikhonova et al, 2019; Zhao et al, 2019). CAR cells are composed of two major groups: pre‐adipocyte‐like reticular cells (Adipo‐CAR cells) and pre‐osteoblast‐like cells (Osteo‐CAR cells) (Baccin et al, 2020; Matsushita, Nagata, et al, 2020; Matsushita, Chu, et al, 2021). The Adipo‐CAR cell‐specific marker Cxcl12‐creER line revealed that Cxcl12‐creER + cells are located preferentially in the central marrow space as dormant cells and do not contribute to cortical osteoblasts, even after a long chase under physiological conditions.…”

Section: Sscs and Their Cell Fate In Physiological And Regenerative C...mentioning

confidence: 99%

Bone regeneration: A message from clinical medicine and basic science

Tsukagoshi

2022

Clinical Anatomy

Self Cite

View full text Add to dashboard Cite

Population aging is a global phenomenon and with it, the number of bone fractures increases due to higher incidences of osteoporosis. Bone fractures in the elderly increase the risk of bedridden status and mortality. Therefore, the control of osteoporosis and bone fracture is important for healthy life expectancy, and the fundamental understanding of its pathogenesis and its application in treatment is of great social significance. To solve these clinical problems, it is necessary to integrate clinical medicine and basic research. Bone regeneration after a fracture is an essential function of the living body. The prevailing view is that a small number of resident skeletal stem cells are solely responsible for regenerative capacity. Although these cells have long been considered to be in the bone marrow, it has been shown that they are also present in the growth plate and periosteum. More recently, distinct types of cells in the bone marrow, including bone marrow stromal cells, osteoblast progenitor cells, and osteoblasts, have been shown to participate in bone regeneration. Interestingly, the cellular plasticity of differentiated cells, rather than active recruitment of resident stem cell populations, may largely account for regeneration of bone tissues; terminally differentiated cells de-differentiate into a stem cell-like state, and then redifferentiate into regenerating bone. In this review, we discuss the clinical risk and preventive therapy of bone fractures and the current concept of bone regeneration in basic mechanical insights, which may prove useful to both clinicians and researchers.

show abstract

Intercellular Interactions of an Adipogenic CXCL12-Expressing Stromal Cell Subset in Murine Bone Marrow

Cited by 16 publications

References 48 publications

The fate of early perichondrial cells in developing bones

The fate of early perichondrial cells in developing bones

Toward Marrow Adipocytes: Adipogenic Trajectory of the Bone Marrow Stromal Cell Lineage

Bone regeneration: A message from clinical medicine and basic science

Contact Info

Product

Resources

About