Exogenous Activation of Wnt/β-Catenin Signaling Attenuates Binge Alcohol-Induced Deficient Bone Fracture Healing

Lauing, Kristen L.; Sundaramurthy, Sumana; Nauer, Rachel K.; Callaci, John J.

doi:10.1093/alcalc/agu006

Cited by 32 publications

(28 citation statements)

References 39 publications

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“…Besides, it is possible that the β‐catenin mRNA has been degraded when the β‐catenin protein reaches its peak. Studies have also successfully utilized Licl to activate Wnt/β‐catenin signaling both in vivo and in vitro . We showed that activation of Wnt/β‐catenin signaling by Licl attenuated d ‐gal‐induced apoptosis and neurodegeneration in the rat auditory cortex.…”

Section: Discussionmentioning

confidence: 96%

Activation of Wnt/β‐catenin signaling by lithium chloride attenuates d‐galactose‐induced neurodegeneration in the auditory cortex of a rat model of aging

et al. 2017

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Degeneration of the central auditory system, which is characterized by reduced understanding of speech and source localization of sounds, is an important cause of age‐related hearing loss (presbycusis). Accumulating evidence has demonstrated that Wnt/β‐catenin signaling plays an essential role in the development of the auditory system but its potential role in presbycusis remains unclear. In this study, we used a rat model of aging, created by chronic systemic exposure to d ‐galactose ( d ‐gal), and explored changes in Wnt/β‐catenin signaling in the auditory cortex. A decrease in Wnt/β‐catenin signaling in the auditory cortex was found in both naturally aging and d ‐gal‐mimetic aging rats, as indicated by increased GSK 3β activity and decreased β‐catenin activity. Moreover, lithium chloride (Licl), an activator of Wnt signaling pathway, was administered long term to 15‐month‐old d ‐gal‐treated rats. Activation of Wnt/β‐catenin signaling by Licl attenuated d ‐gal‐induced auditory cortex apoptosis and neurodegeneration. Bmi1, a transcription factor implicated in antiaging and resistance to apoptosis, can be modulated by β‐catenin activity. Here, we showed that the expression of Bmi1 was reduced and the expression of its downstream genes, p16 INK 4a , p19 Arf , and p53 were increased in the auditory cortex both of naturally aging and d ‐gal‐mimetic aging rats. In addition, Licl significantly increased Bmi1 expression and reduced p16 INK 4a , p19 Arf , and p53 expression. Our results indicated that decreased Wnt/β‐catenin signaling might participate in the pathogenesis of central presbycusis through modulating the expression of Bmi1. Wnt/β‐catenin signaling might be used as a potential therapeutic target against presbycusis.

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Section: Discussionmentioning

confidence: 96%

Activation of Wnt/β‐catenin signaling by lithium chloride attenuates d‐galactose‐induced neurodegeneration in the auditory cortex of a rat model of aging

et al. 2017

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“…In mice with the tibia fracture, alcohol slowed the formation of cartilage, reduced the formation of active βcatenin and increased the level of inactive βcatenin. Lithium decreased the GSK3β activity in cartilage, increased the activity of βcatenin and restored the formation of cartilage and its ossification [9]. These findings point out important role of Wnt dependent system to be played in bone growth and bone formation.…”

Section: Abstract: Lithium Glycogen Synthase Kinase 3 β-Amylmentioning

confidence: 52%

Biological effects of lithium – fundamental and medical aspects

Mikosha¹,

Kovzun²,

Тronko³

2017

Ukr.Biochem.J.

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“…In recent years, lithium has gained attention as a potential adjunct for bone healing. Lauing et al treated alcohol‐exposed, tibial shaft fractured mice with 100 mg/kg lithium between days 4 and 14. At 14 days, the alcohol + lithium treated group had restored callus healing similar to healthy mice receiving lithium.…”

Section: Discussionmentioning

confidence: 99%

Low‐dose lithium regimen enhances endochondral fracture healing in osteoporotic rodent bone

Vachhani

Whyne

Wang

et al. 2017

Journal Orthopaedic Research

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Osteoporotic bone fractures are highly prevalent and involve lengthy recovery. Lithium, commonly used in psychiatric medicine, inhibits glycogen synthase kinase-3β in the Wnt/β-catenin pathway, leading to up-regulation of osteogenesis. Our recent preclinical work demonstrated that a 20 mg/kg lithium dose administered beginning 7 days post-fracture for 14 days optimally improved femoral fracture healing in healthy rats at 4 weeks post fracture (46% higher torsional strength). In this study, lithium treatment was evaluated for healing of osteoporotic bone fractures. Six-month-old ovariectomized rats were subjected to closed, load-drop induced femoral diaphyseal fracture. Two regimens involving treatment initiation on day 7 and day 10, respectively, 20 mg/kg/day oral dose and 14 days duration were evaluated. Femurs of lithium- vs. saline- treated rats were analyzed at 4 weeks (for day 7 onset regimen) or 6 weeks (for day 10 onset regimen) post-fracture by stereology and torsional mechanical testing. Initiation on day 10 led to a significant 50% higher maximum yield torque (primary outcome measure) at 6 weeks (309 vs. 206 N-mm, p = 0.005; n = 7, 7). Initiation on day 7 suggested a trend toward a more modest improvement in maximum yield torque (13%) evaluated at 4 weeks post-fracture (234 vs. 206 N-mm, p = 0.10; n = 10, 13). Qualitatively, lithium-treated femurs demonstrated better periosteal and mineralized callus bridging in the day 10 initiation group. Lithium is a widely-available, orally administered, low-cost drug, which represents a feasible pharmacological intervention for both healthy and osteoporotic fracture healing. This study provides important guidelines for future clinical evaluation of lithium in osteoporotic fracture patients. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1783-1789, 2018.

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Exogenous Activation of Wnt/β-Catenin Signaling Attenuates Binge Alcohol-Induced Deficient Bone Fracture Healing

Cited by 32 publications

References 39 publications

Activation of Wnt/β‐catenin signaling by lithium chloride attenuates d‐galactose‐induced neurodegeneration in the auditory cortex of a rat model of aging

Activation of Wnt/β‐catenin signaling by lithium chloride attenuates d‐galactose‐induced neurodegeneration in the auditory cortex of a rat model of aging

Biological effects of lithium – fundamental and medical aspects

Low‐dose lithium regimen enhances endochondral fracture healing in osteoporotic rodent bone

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