Multitasking by the OC Lineage during Bone Infection: Bone Resorption, Immune Modulation, and Microbial Niche

Roper, Philip M.; Shao, Christine; Veis, Deborah J.

doi:10.3390/cells9102157

Cited by 21 publications

(10 citation statements)

References 112 publications

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“…IL-1b also increases RANKL production in osteocytes and osteoblasts, promoting osteoclastogenesis (103)(104)(105). Moreover, IL-1b elevates M-CSF levels and decreases OPG levels (106,107). IL-1b-triggered chemokines, such as CX3CL1, in osteoblasts regulate osteoclast precursor migration and differentiation (108).…”

Section: Inflammasomes and Osteoclastsmentioning

confidence: 99%

“…Appropriate inflammasome activity is critical in bone healing and new bone formation, as the ASC knockout mice with tibia defect exhibit delayed osteoblast differentiation compared with their wild-type counterparts ( 8 ). When inflammasomes are activated, osteoblasts promote osteoclastogenesis via increased production of cytokines and chemokines, such as RANKL and CX3CL1, or decreased OPG levels, as described above ( 107 ). IL-1β also affects osteoblast arrangement ( 143 ).…”

Section: Mechanisms Of Bone Loss Related To Inflammasomesmentioning

confidence: 99%

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Inflammasomes in Alveolar Bone Loss

Ling

Jiang

2021

Front. Immunol.

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Bone remodeling is tightly controlled by osteoclast-mediated bone resorption and osteoblast-mediated bone formation. Fine tuning of the osteoclast–osteoblast balance results in strict synchronization of bone resorption and formation, which maintains structural integrity and bone tissue homeostasis; in contrast, dysregulated bone remodeling may cause pathological osteolysis, in which inflammation plays a vital role in promoting bone destruction. The alveolar bone presents high turnover rate, complex associations with the tooth and periodontium, and susceptibility to oral pathogenic insults and mechanical stress, which enhance its complexity in host defense and bone remodeling. Alveolar bone loss is also involved in systemic bone destruction and is affected by medication or systemic pathological factors. Therefore, it is essential to investigate the osteoimmunological mechanisms involved in the dysregulation of alveolar bone remodeling. The inflammasome is a supramolecular protein complex assembled in response to pattern recognition receptors and damage-associated molecular patterns, leading to the maturation and secretion of pro-inflammatory cytokines and activation of inflammatory responses. Pyroptosis downstream of inflammasome activation also facilitates the clearance of intracellular pathogens and irritants. However, inadequate or excessive activity of the inflammasome may allow for persistent infection and infection spreading or uncontrolled destruction of the alveolar bone, as commonly observed in periodontitis, periapical periodontitis, peri-implantitis, orthodontic tooth movement, medication-related osteonecrosis of the jaw, nonsterile or sterile osteomyelitis of the jaw, and osteoporosis. In this review, we present a framework for understanding the role and mechanism of canonical and noncanonical inflammasomes in the pathogenesis and development of etiologically diverse diseases associated with alveolar bone loss. Inappropriate inflammasome activation may drive alveolar osteolysis by regulating cellular players, including osteoclasts, osteoblasts, osteocytes, periodontal ligament cells, macrophages, monocytes, neutrophils, and adaptive immune cells, such as T helper 17 cells, causing increased osteoclast activity, decreased osteoblast activity, and enhanced periodontium inflammation by creating a pro-inflammatory milieu in a context- and cell type-dependent manner. We also discuss promising therapeutic strategies targeting inappropriate inflammasome activity in the treatment of alveolar bone loss. Novel strategies for inhibiting inflammasome signaling may facilitate the development of versatile drugs that carefully balance the beneficial contributions of inflammasomes to host defense.

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Section: Inflammasomes and Osteoclastsmentioning

confidence: 99%

Section: Mechanisms Of Bone Loss Related To Inflammasomesmentioning

confidence: 99%

Inflammasomes in Alveolar Bone Loss

Ling

Jiang

2021

Front. Immunol.

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“…Key characteristics of osteomyelitis are severe inflammation, vascular impairment, and localized bone loss and destruction (2). The host responds to the presence of bacteria such as S. aureus by releasing inflammatory factors and degradative enzymes from immune cells, which contribute to the destruction of bone matrix and bone trabeculae (1,(5)(6)(7)(8)(9)(10). Many of the innate immune responses involved in antibacterial host defense also have significant impacts on bone homeostasis, and the release of inflammatory mediators at the infection site can result in decreased osteoblast-mediated bone formation and increased osteoclast activation and bone resorption, thereby promoting bone loss.…”

Section: The Development Of Chronic Osteomyelitismentioning

confidence: 99%

Mechanisms of Antibiotic Failure During Staphylococcus aureus Osteomyelitis

Gimza

Cassat

2021

Front. Immunol.

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Staphylococcus aureus is a highly successful Gram-positive pathogen capable of causing both superficial and invasive, life-threatening diseases. Of the invasive disease manifestations, osteomyelitis or infection of bone, is one of the most prevalent, with S. aureus serving as the most common etiologic agent. Treatment of osteomyelitis is arduous, and is made more difficult by the widespread emergence of antimicrobial resistant strains, the capacity of staphylococci to exhibit tolerance to antibiotics despite originating from a genetically susceptible background, and the significant bone remodeling and destruction that accompanies infection. As a result, there is a need for a better understanding of the factors that lead to antibiotic failure in invasive staphylococcal infections such as osteomyelitis. In this review article, we discuss the different non-resistance mechanisms of antibiotic failure in S. aureus. We focus on how bacterial niche and destructive tissue remodeling impact antibiotic efficacy, the significance of biofilm formation in promoting antibiotic tolerance and persister cell formation, metabolically quiescent small colony variants (SCVs), and potential antibiotic-protected reservoirs within the substructure of bone.

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“…The net inflammatory reaction in the infection condition is shown in Figure 3 with a light red background. Inflammasome activation greatly contributes to bone resorption by upregulating osteoclast activity ( Roper et al, 2020 ; Jin et al, 2021 ). Osteoclasts are derived from the monocyte-macrophage lineage in bone marrow and mediate bone resorption.…”

Section: Turnover Homeostasis-based Bone-targeted Therapeutic Strateg...mentioning

confidence: 99%

Mini Review Therapeutic Strategies Targeting for Biofilm and Bone Infections

Wu²,

Liu³

et al. 2022

Front. Microbiol.

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Bone infection results in a complex inflammatory response and bone destruction. A broad spectrum of bacterial species has been involved for jaw osteomyelitis, hematogenous osteomyelitis, vertebral osteomyelitis or diabetes mellitus, such as Staphylococcus aureus (S. aureus), coagulase-negative Staphylococcus species, and aerobic gram-negative bacilli. S. aureus is the major pathogenic bacterium for osteomyelitis, which results in a complex inflammatory response and bone destruction. Although various antibiotics have been applied for bone infection, the emergence of drug resistance and biofilm formation significantly decrease the effectiveness of those agents. In combination with gram-positive aerobes, gram-negative aerobes and anaerobes functionally equivalent pathogroups interact synergistically, developing as pathogenic biofilms and causing recurrent infections. The adhesion of biofilms to bone promotes bone destruction and protects bacteria from antimicrobial agent stress and host immune system infiltration. Moreover, bone is characterized by low permeability and reduced blood flow, further hindering the therapeutic effect for bone infections. To minimize systemic toxicity and enhance antibacterial effectiveness, therapeutic strategies targeting on biofilm and bone infection can serve as a promising modality. Herein, we focus on biofilm and bone infection eradication with targeting therapeutic strategies. We summarize recent targeting moieties on biofilm and bone infection with peptide-, nucleic acid-, bacteriophage-, CaP- and turnover homeostasis-based strategies. The antibacterial and antibiofilm mechanisms of those therapeutic strategies include increasing antibacterial agents’ accumulation by bone specific affinity, specific recognition of phage-bacteria, inhibition biofilm formation in transcription level. As chronic inflammation induced by infection can trigger osteoclast activation and inhibit osteoblast functioning, we additionally expand the potential applications of turnover homeostasis-based therapeutic strategies on biofilm or infection related immunity homeostasis for host-bacteria. Based on this review, we expect to provide useful insights of targeting therapeutic efficacy for biofilm and bone infection eradication.

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Multitasking by the OC Lineage during Bone Infection: Bone Resorption, Immune Modulation, and Microbial Niche

Cited by 21 publications

References 112 publications

Inflammasomes in Alveolar Bone Loss

Inflammasomes in Alveolar Bone Loss

Mechanisms of Antibiotic Failure During Staphylococcus aureus Osteomyelitis

Mini Review Therapeutic Strategies Targeting for Biofilm and Bone Infections

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