Osteoimmunological Characterization of Borrelia burgdorferi-Induced Bone Loss: From Phenotype to Molecular Mechanisms

Lyme disease (LD) is one of the most prevalent tick-borne infections in the North American region. The causative organism of LD, Borrelia burgdorferi (B. burgdorferi), is transmitted to the host (animals or humans) via the bite of Ixodes tick. B. burgdorferi is highly motile and disseminates to various tissues, including bone. B. burgdorferi induces trabecular long bone loss in murine models, but its phenotype and molecular mechanisms remain unknown. Furthermore, it is not known if B. burgdorferi induces loss of alveolar bone (supporting teeth). We first conducted an extensive literature review on the impact of various tick-borne infections on the bone. We reported that LD is the only vector-borne disease for which murine bone loss has been documented in the literature. We then conducted an in-vivo murine study to characterize the bone loss phenotype associated with B. burgdorferi infection at various stages of infection. We demonstrated that significant trabecular long bone loss (males > females) occurred in mice four weeks after infection, but it was resolved by eight weeks. Long bone loss was associated with reduced osteoblast numbers, but not with increased osteoclast numbers or bacterial burden in the bone. We also observed progressive non-transient alveolar bone loss (similar for both sexes) in infected mice. As bacterial burden was not associated with significant long bone loss, we hypothesized that alveolar bone loss could be related to infection-induced systemic inflammation driven by pro-inflammatory cytokines such as interleukin-6 (IL-6). To explore the molecular mechanisms behind non-repairable alveolar bone loss, we conducted another in-vivo study, which demonstrated that although B. burgdorferi was not detected in the alveolar bones, WT infected mice suffered significantly more alveolar bone loss than IL-6 deficient mice post-infection and it was associated with the suppression of osteoblastogenesis rather than increased osteoclastogenesis or bacterial burden. Collectively, these findings suggest that humans infected with B. burgdorferi may experience transient trabecular long bone loss and permanent loss of the alveolar bone. Modulating IL-6-driven bone loss pathways may help preserve alveolar bone integrity and reduce the risk of tooth loss, but clinical studies of periodontitis and alveolar bone loss in humans are warranted.

Department dc:contributor.department

Dentistry

Year dc:date.issued

2025

Author dc:creator

• Farooq, Imran

Advisor dc:contributor.advisor

• Moriarty, Tara Dr.

• Bone
• Borrelia burgdorferi
• Infectious disease
• Interleukin-6
• Lyme disease
• Tick borne disease

Handle dc:identifier.uri

https://hdl.handle.net/1807/150429

OAI identifier oai:identifier

oai:utoronto.scholaris.ca:1807/150429