IL-34 exacerbates pathogenic features of Alzheimer’s disease and calvaria osteolysis in triple transgenic (3x-Tg) female mice

Ho, Anny; Ngala, Bidii; Yamada, Chiaki; Garcia, Christopher; Duarte, Carolina; Akkaoui, Juliet; Ciolac, Dumitru; Nusbaum, Amilia; Kochen, William; Efremova, Daniela; Groppa, Stanislav; Nathanson, Lubov; Bissel, Stephanie; Oblak, Adrian; Kacena, Melissa A.; Movila, Alexandru

doi:10.1016/j.biopha.2023.115435

Cited by 5 publications

(3 citation statements)

References 74 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Published clinical observations have shown the role of IL-34 as a possible mediator for inflammatory rheumatoid arthritis, osteosarcoma, and multiple myeloma (Baghdadi et al, 2019;Chemel et al, 2012;Franze et al, 2020;Hwang et al, 2012;Segaliny et al, 2015). Furthermore, our recently published study reported that IL-34 exacerbates calvaria osteolysis in female triple-transgenic Alzheimer's disease mice (Ho et al, 2023). The results found in this study also demonstrate the clinical significance of further evaluating intraoral GCF and salivary levels of IL-34 in periodontitis patients compared to periodontally healthy ones (Batra et al, 2019;Guruprasad & Pradeep, 2018a).…”

Section: Discussionsupporting

confidence: 74%

Effects of IL‐34 and anti‐IL‐34 neutralizing mAb on alveolar bone loss in a ligature‐induced model of periodontitis

Duarte,

Yamada,

Ngala

et al. 2023

Molecular Oral Microbiology

Self Cite

View full text Add to dashboard Cite

Macrophage colony‐stimulating factor (M‐CSF) and interleukin‐34 (IL‐34) are ligands for the colony‐stimulating factor‐1 receptor (CSF‐1r) expressed on the surface of monocyte/macrophage lineage cells. The importance of coordinated signaling between M‐CSF/receptor activator of the nuclear factor kappa‐Β ligand (RANKL) in physiological and pathological bone remodeling and alveolar bone loss in response to oral bacterial colonization is well established. However, our knowledge about the IL‐34/RANKL signaling in periodontal bone loss remains limited. Recently published cohort studies have demonstrated that the expression patterns of IL‐34 are dramatically elevated in gingival crevicular fluid collected from patients with periodontitis. Therefore, the present study aims to evaluate the effects of IL‐34 on osteoclastogenesis in vitro and in experimental ligature‐mediated model of periodontitis using male mice. Our initial in vitro study demonstrated increased RANKL‐induced osteoclastogenesis of IL‐34‐primed osteoclast precursors (OCPs) compared to M‐CSF‐primed OCPs. Using an experimental model of ligature‐mediated periodontitis, we further demonstrated elevated expression of IL‐34 in periodontal lesions. In contrast, M‐CSF levels were dramatically reduced in these periodontal lesions. Furthermore, local injections of mouse recombinant IL‐34 protein significantly elevated cathepsin K activity, increased the number of tartrate‐resistant acid phosphatase (TRAP)‐positive osteoclasts and promoted alveolar bone loss in periodontitis lesions. In contrast, anti‐IL‐34 neutralizing monoclonal antibody significantly reduced the level of alveolar bone loss and the number of TRAP‐positive osteoclasts in periodontitis lesions. No beneficial effects of locally injected anti‐M‐CSF neutralizing antibody were observed in periodontal lesions. This study illustrates the role of IL‐34 in promoting alveolar bone loss in periodontal lesions and proposes the potential of anti‐IL34 monoclonal antibody (mAb)‐based therapeutic regimens to suppress alveolar bone loss in periodontitis lesions.

show abstract

Section: Discussionsupporting

confidence: 74%

Effects of IL‐34 and anti‐IL‐34 neutralizing mAb on alveolar bone loss in a ligature‐induced model of periodontitis

Duarte,

Yamada,

Ngala

et al. 2023

Molecular Oral Microbiology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Males and females of 3x‐Tg mice and their wild‐type strain (3‐month‐old) were used in this study ( n = 5 animals/sex/condition). We and others recently confirmed that inflammatory osteolysis and experimental periodontitis promotes memory and cognitive decline in 3x‐Tg mice 23,24 . Mice were kept in a conventional room with a 12‐h light–dark cycle at a constant temperature.…”

Section: Methodsmentioning

confidence: 96%

“…Since transgenic mouse models are critical for understanding the development and progression of dementia and periodontitis, 20 an urgent need exists to validate new pre‐clinical models of dementia that recapitulate the impact of sex on the key pathogenic hallmarks of human periodontitis complicated by dementia, including Alzheimer's disease. Among the known experimental models of dementia, the triple transgenic (3x‐Tg) dementia‐like mice feature three human mutations, the Swedish APP mutation (KM670/671NL), the PSEN1 M146V mutation, and the MAPT P301L 21 and simultaneously demonstrate amyloid and tau pathologies associated with sexual dimorphism, with elevated dementia prevalence in female mice 22,23 …”

Section: Introductionmentioning

confidence: 99%

Dementia exacerbates periodontal bone loss in females

Yamada,

Ho,

Garcia

et al. 2024

J of Periodontal Research

Self Cite

View full text Add to dashboard Cite

BackgroundPeriodontitis is a chronic inflammatory disease defined by the pathologic loss of the periodontal ligament and alveolar bone in relation to aging. Although clinical cohort studies reported that periodontitis is significantly elevated in males compared to females, emerging evidence indicates that females with dementia are at a greater risk for periodontitis and decreased alveolar bone.ObjectiveThis study aimed to evaluate whether dementia is a potential sex‐dependent risk factor for periodontal bone loss using an experimental model of periodontitis induced in the triple transgenic (3x‐Tg) dementia‐like mice and clinical samples collected from senior 65 plus age patients with diagnosed dementia.Materials and MethodsWe induced periodontitis in dementia‐like triple‐transgenic (3x‐Tg) male and female mice and age‐matched wild‐type (WT) control mice by ligature placement. Then, alveolar bone loss and osteoclast activity were evaluated using micro‐CT and in situ imaging assays. In addition, we performed dental examinations on patients with diagnosed dementia. Finally, dementia‐associated Aβ42 and p‐Tau (T181) and osteoclastogenic receptor activator of nuclear factor kappa‐Β ligand (RANKL) in gingival crevicular fluid (GCF) collected from mice and clinical samples were measured by enzyme‐linked immunosorbent assay (ELISA).ResultsAlveolar bone loss and in situ osteoclast activity were significantly elevated in periodontal lesions of 3x‐Tg females but not males, compared to wild‐type control mice. In addition, we also observed that the probing pocket depth (PPD) was also significantly elevated in female patients with dementia. Using ELISA assay, we observed that females had elevated levels of osteoclastogenic RANKL and dementia‐associated Aβ42 and p‐Tau (T181) in the GCF collected from experimental periodontitis lesions and clinical samples.ConclusionAltogether, we demonstrate that females with dementia have an increased risk for periodontal bone loss compared to males.

show abstract

“Three birds, one stone” strategy of NIR-responsive CO/H2S dual-gas Nanogenerator for efficient treatment of osteoporosis

Yang,

Ye,

Wang

et al. 2024

Materials Today Bio

View full text Add to dashboard Cite

IL-34 exacerbates pathogenic features of Alzheimer’s disease and calvaria osteolysis in triple transgenic (3x-Tg) female mice

Cited by 5 publications

References 74 publications

Effects of IL‐34 and anti‐IL‐34 neutralizing mAb on alveolar bone loss in a ligature‐induced model of periodontitis

Effects of IL‐34 and anti‐IL‐34 neutralizing mAb on alveolar bone loss in a ligature‐induced model of periodontitis

Dementia exacerbates periodontal bone loss in females

“Three birds, one stone” strategy of NIR-responsive CO/H2S dual-gas Nanogenerator for efficient treatment of osteoporosis

Contact Info

Product

Resources

About