Lactoferrin inhibits infection-related osteoclastogenesis without interrupting compressive force-related osteoclastogenesis

Inubushi, Toshihiro; Kawazoe, Aki; Miyauchi, Mutsumi; Yanagisawa, S.; Subarnbhesaj, Ajiravudh; Chea, Chanbora; Ayuningtyas, Nurina Febriyanti; Ishikado, Atsushi; Tanaka, Eiji; Takata, Takashi

doi:10.1016/j.archoralbio.2013.11.002

Cited by 9 publications

(6 citation statements)

References 29 publications

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“…CTSK, a specific osteoclast marker (Dai et al, 2020), was examined to assess osteoclast alteration. Consistent with a previous finding (Cheng et al, 2018), its inhibitory role in osteoclastogenesis was observed only at high concentrations (1 g/kg) group, which was not consonant with studies conducted by Kawazoe et al (Inubushi et al, 2014; Kawazoe et al, 2013). The inconsistency may be derived from different animal models, diverse LF forms, and various modes of LF administration.…”

Section: Discussionsupporting

confidence: 86%

Gavage‐administered lactoferrin promotes palatal expansion stability in a dose‐dependent manner

et al. 2021

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Objective To investigate the effects of different lactoferrin concentrations on mid‐palatal suture bone remodeling during palatal expansion and relapse in rats. Materials and Methods Thirty‐two 5‐week‐old male Wistar rats were randomly divided into four groups: EO (expansion only), E+LF1 (expansion plus 10 mg/kg/day daily LF), E+LF2 (expansion plus 100 mg/kg/day daily LF), and E+LF3 (expansion plus 1 g/kg/day daily LF). Thereafter, micro‐computed tomography and micro‐morphology of the mid‐palatal suture were analyzed on day 7 and day 14, respectively. Results The arch widths were increased in all the four groups after expansion, and there was no significant difference among them on day 7. After relapse, however, the arch width in the E+LF3 group was significantly larger compared with EO group. In E+LF3 group and E+LF2 group, new bone formation and osteoblast number were enhanced with up‐regulated expression of osteocalcin and collagen type I, while the expression of cathepsin K‐positive cells was downregulated in E+LF3 group. Conclusion Lactoferrin gavage administration might increase the stability of palatal expansion and reduce relapse in a concentration‐dependent manner by enhancing bone formation and inhibiting resorption. LF administration may be promising for optimizing the maxillary expansion outcome.

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Section: Discussionsupporting

confidence: 86%

Gavage‐administered lactoferrin promotes palatal expansion stability in a dose‐dependent manner

et al. 2021

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“…Lipopolysaccharide (LPS) is the main virulence factor in Gram‐negative bacteria. It can induce an inflammatory response and can induce osteoclast formation in RAW 264.7 macrophage cells in the absence of RANKL (Inubushi et al, ; Islam et al, ). LTA is the main virulence factor in Gram‐positive bacteria, and it is also the virulence factor in E. faecalis refractory apical periodontitis.…”

Section: Discussionmentioning

confidence: 99%

JAK2‐STAT3 signaling pathway is involved in rat periapical lesions induced by Enterococcus faecalis

Wang

Jin

et al. 2019

Oral Diseases

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Objectives This study aimed to investigate the role of JAK2‐STAT3 (Janus kinase 2/signal transducer and activator of transcription 3) in periapical disease caused by Enterococcus faecalis, as well as the correlation between lipoteichoic acid (LTA) in E. faecalis and the activity of the JAK2‐STAT3 signaling pathway and osteoclast formation. Materials and Methods A rat model of periapical periodontitis induced by E. faecalis was established. Periapical bone resorption was confirmed by HE staining. The expression of JAK2, p‐JAK2, STAT3, and p‐STAT3 was assessed with immunohistochemical staining. Osteoclasts were observed through enzyme histochemical staining. LTA acted on mouse osteoclast precursor cells (RAW264.7 cells); a JAK2 inhibitor (AG490) was used to inhibit the JAK2‐STAT3 pathway in RAW264.7 cells. The expression of proteins in the JAK2‐STAT3 pathway and TRAP (tartrate resistant acid phosphatase) in RAW264.7 cells was also detected. Results Rat periapical periodontitis was successfully established and bone resorption peaked at day 21. The expression of critical components in the JAK2‐STAT3 pathway increased with the progression of inflammation. LTA promoted the differentiation of RAW264.7 cells into osteoclasts. NFATc1 was highly expressed and was inhibited by AG490. Conclusions JAK2‐STAT3 signaling pathway plays an important role in the process of periapical bone resorption and osteoclastogenesis.

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“…Lipopolysaccharide (LPS), a component of the outer membrane of gram-negative bacteria, stimulates osteoclastogenesis (the formation of bone-destroying cells) by activating the RANKL signaling pathway in bone marrow cells. In mouse bone marrow cells, Lf inhibited LPS-induced osteoclastogenesis dose-dependently ( 9 ). When human peripheral CD14+ monocyte and macrophage cells were induced to differentiate into osteoclasts by a cocktail of macrophage colony-stimulating factor (M-CSF) and RANKL, Lf suppressed the expression of genes and proteins involved in osteoclast differentiation and activity such as TRAP and cathepsin K.…”

Section: The Regulation Of Bone Cells By Lf and Its Associated Signal...mentioning

confidence: 99%

“…In recent years, there has been growing interest in the potential role of Lf in skeletal homeostasis, particularly in maintaining bone health and treating bone-related disorders such as osteoporosis. Studies have shown that Lf is expressed in bone cells, including osteoblasts and osteoclasts, and can modulate bone metabolism by promoting osteoblast differentiation and mineralization, inhibiting osteoclast activity, and regulating bone remodeling ( 5 , 8 , 9 ). The anti-inflammatory ( 10 ) and antioxidant ( 11 ) effects of Lf could contribute to its salutary effects on bone health.…”

Section: Introductionmentioning

confidence: 99%

The role of lactoferrin in bone remodeling: evaluation of its potential in targeted delivery and treatment of metabolic bone diseases and orthopedic conditions

Tian,

Han,

Yang

et al. 2023

Front. Endocrinol.

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Lactoferrin (Lf) is a multifunctional protein that is synthesized endogenously and has various biological roles including immunological regulation, antibacterial, antiviral, and anticancer properties. Recently, research has uncovered Lf’s critical functions in bone remodeling, where it regulates the function of osteoblasts, chondrocytes, osteoclasts, and mesenchymal stem cells. The signaling pathways involved in Lf’s signaling in osteoblasts include (low density lipoprotein receptor-related protein – 1 (LRP-1), transforming growth factor β (TGF-β), and insulin-like growth factor – 1 (IGF-1), which activate downstream pathways such as ERK, PI3K/Akt, and NF-κB. These pathways collectively stimulate osteoblast proliferation, differentiation, and mineralization while inhibiting osteoclast differentiation and activity. Additionally, Lf’s inhibitory effect on nuclear factor kappa B (NF-κB) suppresses the formation and activity of osteoclasts directly. Lf also promotes chondroprogenitor proliferation and differentiation to chondrocytes by activating the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) and phosphoinositide 3-kinase/protein kinase B(PI3K/Akt)signaling pathways while inhibiting the expression of matrix-degrading enzymes through the suppression of the NF-κB pathway. Lf’s ability to stimulate osteoblast and chondrocyte activity and inhibit osteoclast function accelerates fracture repair, as demonstrated by its effectiveness in animal models of critical-sized long bone defects. Moreover, studies have indicated that Lf can rescue dysregulated bone remodeling in osteoporotic conditions by stimulating bone formation and suppressing bone resorption. These beneficial effects of Lf on bone health have led to its exploration in nutraceutical and pharmaceutical applications. However, due to the large size of Lf, small bioactive peptides are preferred for pharmaceutical applications. These peptides have been shown to promote bone fracture repair and reverse osteoporosis in animal studies, indicating their potential as therapeutic agents for bone-related diseases. Nonetheless, the active concentration of Lf in serum may not be sufficient at the site requiring bone regeneration, necessitating the development of various delivery strategies to enhance Lf’s bioavailability and target its active concentration to the site requiring bone regeneration. This review provides a critical discussion of the issues mentioned above, providing insight into the roles of Lf in bone remodeling and the potential use of Lf as a therapeutic target for bone disorders.

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Lactoferrin inhibits infection-related osteoclastogenesis without interrupting compressive force-related osteoclastogenesis

Cited by 9 publications

References 29 publications

Gavage‐administered lactoferrin promotes palatal expansion stability in a dose‐dependent manner

Gavage‐administered lactoferrin promotes palatal expansion stability in a dose‐dependent manner

JAK2‐STAT3 signaling pathway is involved in rat periapical lesions induced by Enterococcus faecalis

The role of lactoferrin in bone remodeling: evaluation of its potential in targeted delivery and treatment of metabolic bone diseases and orthopedic conditions

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