C3a-C3aR signaling is a novel modulator of skeletal homeostasis

Kuhn, Megan B.; VandenBerg, Hayden S.; Reynolds, Andrew; Carson, Matthew D.; Warner, Amy J.; LaRue, Amanda C.; Novince, Chad M.; Hathaway‐Schrader, Jessica D.

doi:10.1016/j.bonr.2023.101662

Bone Reports

2023

DOI: 10.1016/j.bonr.2023.101662

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C3a-C3aR signaling is a novel modulator of skeletal homeostasis

Megan B. Kuhn

Hayden S. VandenBerg

Andrew Reynolds

et al.

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2024

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Cellular signatures in human blood track bone mineral density in postmenopausal women

Kaneko,

Tsai,

Meñez

et al. 2024

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Osteoclasts are the sole bone-resorbing cells and are formed by the fusion of osteoclast precursor cells (OCPs) derived from myeloid lineage cells. Animal studies reveal that circulating OCPs (cOCPs) in blood travel to bone and fuse with bone-resident osteoclasts. However, the characteristics of human cOCPs and their association with bone diseases remain elusive. We have identified and characterized human cOCPs and found a positive association between cOCPs and osteoclast activity. Sorted cOCPs have a higher osteoclastogenic potential than other myeloid cells and effectively differentiate into osteoclasts. cOCPs exhibit distinct morphology and transcriptomic signatures. The frequency of cOCPs in the blood varies among treatment-naive postmenopausal women and has an inverse correlation with lumbar spine bone density and a positive correlation with serum CTX, a bone resorption marker. The increased cOCPs in treatment-naive patients with osteoporosis were significantly diminished by denosumab, a widely used antiresorptive therapy. Our study reveals the distinctive identity of human cOCPs and the potential link between the dynamic regulation of cOCPs and osteoporosis and its treatment. Taken together, our study enhances our understanding of human cOCPs and highlights a potential opportunity to measure cOCPs through a simple blood test, which could potentially identify high-risk individuals.

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Cellular signatures in human blood track bone mineral density in postmenopausal women

Kaneko,

Tsai,

Meñez

et al. 2024

JCI Insight

View full text Add to dashboard Cite

show abstract

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C3a-C3aR signaling is a novel modulator of skeletal homeostasis

Cited by 1 publication

References 47 publications

Cellular signatures in human blood track bone mineral density in postmenopausal women

Cellular signatures in human blood track bone mineral density in postmenopausal women

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