Age-Dependent Effects of Macrophage Derived Cathelicidin Antimicrobial Peptide on Bone Fracture Repair
CAMP appears to play a dual role in bone repair, promoting healing in young mice but potentially hindering it in aged mice.
Where it sits
this study against the rest of the ll-37 corpusSummary and findings
This study examined the role of cathelicidin antimicrobial peptide (CAMP) in bone fracture repair across different ages in mice. The findings suggest that CAMP expression is higher during fracture healing in young mice compared to aged mice. Depletion of CAMP in young mice delayed fracture repair, while depletion in aged mice increased callus bone formation.
Abstract
The pace of fracture repair declines with age, increasing the risk of delayed union and nonunion. Delayed union and nonunion are associated with significant morbidity and even mortality with few effective non-surgical interventions. Here, we identify cathelicidin antimicrobial peptide (CAMP) as an age-dependent regulator of bone repair. Single-cell RNA sequencing and immunohistochemistry demonstrated higher CAMP expression during fracture healing in young compared with aged mice. Global or myeloid lineage-depletion of Camp delayed fracture repair in young mice, whereas Camp depletion in aged mice increased callus bone formation. Heterochronic bone marrow transplantation using the conditional genetic knockout further implicated hematopoietic-lineage derived cells in these effects and demonstrated that myeloid-specific Camp expression is important in the rejuvenation of the pace of fracture healing. CAMP promotes osteogenic differentiation through P2X7 receptor (P2X7R)-dependent signaling, influencing the downstream regulation of NLRP3 expression. NLRP3 expression is also correlated with osteogenesis following Camp modulation in both young and old mice, supporting CAMP-P2X7R-NLRP3 signaling as a regulator of osteogenesis. Together, these findings identify CAMP as a hematopoietic-derived regulator of bone repair whose function is age-dependent, promoting fracture healing in young animals while constraining it in aged animals.
Background
Not reported in abstract.
Methods
Not reported in abstract.
Results
Not reported in abstract.
Interpretation
Not reported in abstract.
Limitations
Not reported in abstract.