Lymphatic platelet thrombosis limits bone repair by precluding lymphatic transporting DAMPs

ABSTRACT: In the musculoskeletal system, lymphatic vessels (LVs), which are interdigitated with blood vessels, travel and form an extensive transport network. Blood vessels in bone regulate osteogenesis and hematopoiesis, however, whether LVs in bone affect fracture healing is unclear. Here, we investigated the lymphatic draining function at the tibial fracture sites using near-infrared indocyanine green lymphatic imaging (NIR-ICG) and discovered that lymphatic drainage insufficiency (LDI) started on day one and persisted for up to two weeks following the fracture. Sufficient lymphatic drainage facilitates fracture healing. Furthermore, we identified that lymphatic platelet thrombosis (LPT) blocked the draining lymphoid sinus and LVs, caused LDI, and then inhibited fracture healing, which can be rescued by a pharmacological approach. Moreover, unblocked lymphatic drainage decreased neutrophils and increased M2-like macrophages of the hematoma niche to support osteoblast (OB) survival and bone marrow-derived mesenchymal stem cell (BMSC) proliferation via transporting damage-associated molecular patterns (DAMPs). Lymphatic platelet thrombolysis also benefits senile fracture healing. These findings demonstrate that LPT limits bone regeneration by impeding lymphatic transporting DAMPs. Together, these findings represent a novel way forward in the treatment of bone repair.

ORGANISM(S): Rattus Norvegicus

SUBMITTER: Yongjun Wang  

PROVIDER: PXD056584 | iProX | Sat Oct 05 00:00:00 BST 2024

REPOSITORIES: iProX