Old Blood, Young Bones: Identification of Middle-Aged Myeloid Cells That Limit Cortical Bone Loss.

Transplantation of 40-week-old bone marrow into lethally irradiated 8-week-old mice increased mid-shaft femoral cortical bone mass and thickness.

• Micro-CT analyses were used to assess cortical bone parameters
• Recipient mice were 8 weeks old and lethally irradiated prior to transplantation
• Donor bone marrow was sourced from either 8-week-old or 40-week-old mice
• The increase was specifically observed at the mid-shaft femoral cortical bone region

Greater erythro-myeloid progenitor (EMP) to hematopoietic stem cell (HSC) ratios were observed when mice were reconstituted with increasing percentages of middle-aged bone marrow.

• Flow cytometry analyses were used to quantify EMP and HSC populations
• The ratio of EMP to HSC increased proportionally with the percentage of 40-week-old bone marrow used in transplantation
• The authors hypothesized that reduced HSC capacity of 40-week-old bone marrow drives compensatory EMP expansion
• This pattern mirrors hematopoietic development in which EMPs expand before definitive HSC production

Comparative single-cell RNA sequencing identified a CD11B+CD36+ myeloid cell population with enriched expression of bone anabolic cytokines.

• scRNA-Seq analyses were performed comparatively between experimental groups
• CD11B+CD36+ cells were characterized by elevated levels of Wnt ligands, especially Wnt6
• These cells exhibited enriched expression of bone anabolic cytokines
• The population was identified as a distinct myeloid cell type within the transplantation model

CD11B+CD36+ cells were confirmed to be donor-derived myeloid cells through lineage tracing assays.

• Lineage tracing assays were performed to determine the origin of CD11B+CD36+ cells
• The cells were confirmed as donor-derived, not host-derived
• This establishes that the middle-aged bone marrow transplant gives rise to the anabolic myeloid population in recipients

Soluble factors produced by CD11B+CD36+ cells enhance osteogenesis in functional assays.

• Functional assays were used to assess the osteogenic capacity of CD11B+CD36+ cell-derived soluble factors
• The conditioned medium or soluble factors from these cells promoted osteogenesis
• This demonstrates a functional role for CD11B+CD36+ cells in bone anabolism beyond transcriptomic characterization

CD11B, CD36, and Wnt6 mark anabolic macrophages within human bone marrow.

• Human bone marrow samples were analyzed to assess translational relevance
• CD11B/CD36/Wnt6 expression was found to exquisitely mark anabolic macrophages in human bone marrow
• This finding supports conservation of the CD11B+CD36+Wnt6+ anabolic myeloid population between mice and humans