The role of M1 and M2 macrophage polarization in progression of medication-related osteonecrosis of the jaw

Paschalidi, Polytimi; Gkouveris, Ioannis; Soundia, Akrivoula; Kalfarentzos, Evangelos; Vardas, Emmanouil; Georgaki, Maria; Kostakis, George; Erović, Boban M.; Tetradis, Sotirios; Perisanidis, Christos; Nikitakis, Nikolaos G.

doi:10.1007/s00784-020-03602-z

Cited by 26 publications

(26 citation statements)

References 45 publications

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“…Additionally, IL-6 or IL-1α/β deficient mice presented considerably reduced osteonecrosis events [ 61 ]. In accordance, elevated IL6 and reduced IL10 expression levels correlated with advanced MRONJ stages in an immunohistochemical study of both denosumab and BP-treated patients presenting stage I–III MRONJ [ 35 ].…”

Section: Macrophage Involvement In Mronj Pathophysiologymentioning

confidence: 68%

“…Macrophages around osteonecrotic lesions in BP-treated mice demonstrate a heightened inflammatory response. Elevated IL6 and reduced IL10 expression levels are present in tissues of patients treated with BPs or denosumab and correlate with advanced stages of MRONJ, thus pointing to an enhanced pro-inflammatory environment [ 35 ]. CD14 is seen in monocyte/macrophage lineage cells, while CD68 is expressed in mature macrophages and is connected to increased phagocytic activity.…”

Section: Clinical Observations and In Vivo Mronj Animal Modelsmentioning

confidence: 99%

“…In addition, M1 and M2 density is significantly higher in patients under bisphosphonates vs. denosumab treatment. Thus, a high M1/M2 ratio correlates with advanced MRONJ [ 35 ]. Similarly, BRONJ specimens display a significantly higher M1 infiltration compared to controls, thus indicating that an M1 polarization shift may be associated with BRONJ pathogenesis [ 65 ].…”

Section: Clinical Observations and In Vivo Mronj Animal Modelsmentioning

confidence: 99%

“…Cells of the monocyte/macrophage lineage are key players in inflammation, from the early phases of acute response to the late stages of resolution [ 30 , 31 , 32 ]. Macrophages are multifunctional cells involved in complex processes that can exacerbate tissue damage or promote wound healing and, thus, have been investigated in the setting of MRONJ [ 31 , 33 , 34 , 35 ]. Here, we focused our review on the existing evidence of the potential contribution of macrophages in MRONJ pathophysiology.…”

Section: Introductionmentioning

confidence: 99%

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Macrophage Involvement in Medication-Related Osteonecrosis of the Jaw (MRONJ): A Comprehensive, Short Review

Gkouveris

Soundia

Gouveris

et al. 2022

Cancers

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Antiresorptive agents such as bisphosphonates (BP) and denosumab are commonly prescribed for the management of primary bone malignancy, bone metastasis, osteoporosis, Paget disease, or other bone disorders. Medication-related osteonecrosis of the Jaws (MRONJ) is a rare but significant complication of antiresorptive medications. Duration, dose, and antiresorptive potency as well as concomitant diseases, additional medications, and local factors affect MRONJ incidence and severity. MRONJ pathophysiology is still poorly understood. Nevertheless, decreased bone resorption due to osteoclastic inhibition along with trauma, infection/inflammation, or blood supply inhibition are considered synergistic factors for disease development. In addition, previous data research examined the effects of antiresorptive medication on immune system components and introduced potential alterations on immune response as novel elements in MRONJ pathogenesis. Considering that macrophages are the first cells in the nonspecific immune response, it is not surprising that these multifaceted players attracted increased attention in MRONJ research recently. This current review attempted to elucidate the effects of antiresorptive medications on several aspects of macrophage activity in relation to the complex inflammatory microenvironment of MRONJ. Collectively, unravelling the mode of action and extent of macrophages’ potential contribution in MRONJ occurrence will provide novel insight in disease pathogenesis and potentially identify intrinsic therapeutic targets.

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Section: Macrophage Involvement In Mronj Pathophysiologymentioning

confidence: 68%

Section: Clinical Observations and In Vivo Mronj Animal Modelsmentioning

confidence: 99%

Section: Clinical Observations and In Vivo Mronj Animal Modelsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Macrophage Involvement in Medication-Related Osteonecrosis of the Jaw (MRONJ): A Comprehensive, Short Review

Gkouveris

Soundia

Gouveris

et al. 2022

Cancers

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“…Preclinical and clinical data reported on the association of Zo with pro-inflammatory effects and in particular the polarization of M1 macrophages [7,31], which are of particular relevance to the pathogenesis of MRONJs. Infectious events have also been linked with the administration of Be, a monoclonal antibody targeting the vascular endothelial growth factor A and subsequently angiogenesis in cancer patients.…”

Section: Discussionmentioning

confidence: 99%

Pharyngeal spreading of peri-implant infections under antiresorptive/antiangiogenic therapy

et al. 2021

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Objectives To assess the influence of antiresorptive/antiangiogenic therapy on the spreading of peri-implant infections in the pharyngeal region. Material and methods This analysis was based on tissue biopsies obtained from a total of twenty-five albino rats having either received (1) amino-bisphosphonate (Zoledronate) (Zo) (n=4), (2) RANKL inhibitor (Denosumab) (De) (n=4), (3) antiangiogenic medication (Bevacizumab) (Be) (n=4), (4) Zo+Be (n=3), (5) De+Be (n=5), or (6) no medication (Co) (n=5). Drug administration was repeated at 12 weeks. Chronic-type peri-implant infections were induced at titanium implants located in the upper jaws. The surface area (%) of infiltrated connective tissue (ICT) and CD68-positive cells was assessed within the lateral pharyngeal/retropharyngeal connective tissue zone. Results Mean (±SD) and median ICT% values and CD68 counts were markedly highest in the De+Be (11.10±6.04; 11.81; 95% CI − 3.89; 26.11) and De (5.70±5.06; 6.19; 95% CI − 2.34; 13.75) groups, reaching statistical significance for De CD68 counts over the Co (0.18±0.25; 0.18; 95% CI −2.14; 2.51) group. In both De+Be and De groups, the ICTs were occasionally associated with an ulceration of the epithelial compartment. Conclusions Induced peri-implant infections were not associated with any inflammatory lesions in pharyngeal tissues. While these findings were similar under Zo and Be medication, De and De+Be had a marked effect on ICT and CD68 values. The clinical relevance of these adverse findings needs further investigation.

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Collagen scaffolds derived from bovine skin loaded withMSCoptimizedM1macrophages remodeling and chronic diabetic wounds healing

Liu

Yang

Zhao

et al. 2022

Bioengineering & Transla Med

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Owing to the persistent inflammatory microenvironment and unsubstantial dermal tissues, chronic diabetic wounds do not heal easily and their recurrence rate is high. Therefore, a dermal substitute that can induce rapid tissue regeneration and inhibit scar formation is urgently required to address this concern. In this study, we established biologically active dermal substitutes (BADS) by combining novel animal tissue‐derived collagen dermal‐replacement scaffolds (CDRS) and bone marrow mesenchymal stem cells (BMSCs) for the healing and recurrence treatments of chronic diabetic wounds. The collagen scaffolds derived from bovine skin (CBS) displayed good physicochemical properties and superior biocompatibility. CBS loaded with BMSCs (CBS‐MCSs) could inhibit M1 macrophage polarization in vitro. Decreased MMP‐9 and increased Col3 at the protein level were detected in CBS‐MSCs‐treated M1 macrophages, which may be attributed to the suppression of the TNF‐α/NF‐κB signaling pathway (downregulating phospho‐IKKα/β/total IKKα/β, phospho‐IκB/total IκB, and phospho‐NFκB/total NFκB) in M1 macrophages. Moreover, CBS‐MSCs could benefit the transformation of M1 (downregulating iNOS) to M2 (upregulating CD206) macrophages. Wound‐healing evaluations demonstrated that CBS‐MSCs regulated the polarization of macrophages and the balance of inflammatory factors (pro‐inflammatory: IL‐1β, TNF‐α, and MMP‐9; anti‐inflammatory: IL‐10 and TGF‐β3) in db/db mice. Furthermore, CBS‐MSCs facilitated the noncontractile and re‐epithelialized processes, granulation tissue regeneration, and neovascularization of chronic diabetic wounds. Thus, CBS‐MSCs have a potential value for clinical application in promoting the healing of chronic diabetic wounds and preventing the recurrence of ulcers.

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The role of M1 and M2 macrophage polarization in progression of medication-related osteonecrosis of the jaw

Cited by 26 publications

References 45 publications

Macrophage Involvement in Medication-Related Osteonecrosis of the Jaw (MRONJ): A Comprehensive, Short Review

Macrophage Involvement in Medication-Related Osteonecrosis of the Jaw (MRONJ): A Comprehensive, Short Review

Pharyngeal spreading of peri-implant infections under antiresorptive/antiangiogenic therapy

Collagen scaffolds derived from bovine skin loaded withMSCoptimizedM1macrophages remodeling and chronic diabetic wounds healing

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