Increased β-adrenergic signaling promotes fracture healing through callus neovascularization in mice.

Traumatic brain injury (TBI) leads to skeletal changes, including bone loss in the unfractured skeleton, and paradoxically accelerates healing of bone fractures; however, the mechanisms remain unclear. TBI is associated with a hyperadrenergic state characterized by increased norepinephrine release. Here, we identified the β-adrenergic receptor (ADRB2) as a mediator of skeletal changes in response to increased norepinephrine.

Transcript-dependent effects of the CALCA gene on the progression of post-traumatic osteoarthritis in mice.

Osteoarthritis represents a chronic degenerative joint disease with exceptional clinical relevance. Polymorphisms of the CALCA gene, giving rise to either a procalcitonin/calcitonin (PCT/CT) or a calcitonin gene-related peptide alpha (αCGRP) transcript by alternative splicing, were reported to be associated with the development of osteoarthritis. The objective of this study was to investigate the role of both PCT/CT and αCGRP transcripts in a mouse model of post-traumatic osteoarthritis (ptOA).

Tranexamic Acid Attenuates the Progression of Posttraumatic Osteoarthritis in Mice.

Background: Posttraumatic osteoarthritis (OA) is a common disorder associated with a high socioeconomic burden, particularly in young, physically active, and working patients. Tranexamic acid (TXA) is commonly used in orthopaedic trauma surgery as an antifibrinolytic agent to control excessive bleeding. Previous studies have reported that TXA modulates inflammation and bone cell function, both of which are dysregulated during posttraumatic OA disease progression.

The selective norepinephrine reuptake inhibitor reboxetine promotes late-stage fracture healing in mice.

Impaired fracture healing is of high clinical relevance, as up to 15% of patients with long-bone fractures display non-unions. Fracture patients also include individuals treated with selective norepinephrine reuptake inhibitors (SNRI). As SNRI were previously shown to negatively affect bone homeostasis, it remained unclear whether patients with SNRI are at risk of impaired bone healing.

Increased beta2-adrenergic signaling is a targetable stimulus essential for bone healing by promoting callus neovascularization.

Traumatic brain injury (TBI) is associated with a hyperadrenergic state and paradoxically causes systemic bone loss while accelerating fracture healing. Here, we identify the beta2-adrenergic receptor (Adrb2) as a central mediator of these skeletal manifestations. While the negative effects of TBI on the unfractured skeleton can be explained by the established impact of Adrb2 signaling on bone formation, Adrb2 promotes neovascularization of the fracture callus under conditions of high sympathetic tone, including TBI and advanced age.