<scp>BMP</scp>‐2 induces human mononuclear cell chemotaxis and adhesion and modulates monocyte‐to‐macrophage differentiation

Pardali, Evangelia; Makowski, Lena; Leffers, Merle; Borgscheiper, Andreas; Waltenberger, Johannes

doi:10.1111/jcmm.13814

Cited by 28 publications

(34 citation statements)

References 42 publications

(112 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For instance, it has been shown that BMP-2 and PDGF-BB induce monocyte and macrophage chemotaxis (7,8,30,31). In addition, BMP-2 may modulate the polarization of macrophages toward an anti-inflammatory phenotype either positively or negatively (8,32). Nevertheless, one of the major side effects of BMP-2 in clinical use is rampant inflammation (33)(34)(35).…”

Section: Discussionmentioning

confidence: 99%

Enhancing the regenerative effectiveness of growth factors by local inhibition of interleukin-1 receptor signaling

et al. 2020

View full text Add to dashboard Cite

Although growth factors (GFs) are key molecules for regenerative medicine, their use has been limited by issues associated with suboptimal delivery systems and incomplete understanding of their signaling dynamics. Here, we explored how proinflammatory signals affect GF regenerative potential. Using bone regeneration in mouse, we found that the regenerative capacity of two clinically relevant GFs (BMP-2 and PDGF-BB) is impaired by interleukin-1 receptor (IL-1R1). Mechanistically, IL-1R1 activation in bone-forming cells desensitizes them to GFs and accelerates senescence. Moreover, administration of the GFs triggers IL-1 release by macrophages. To provide localized and sustained IL-1R1 inhibition, we engineered IL-1R antagonist (IL-1Ra) to bind the extracellular matrix (ECM) very strongly and demonstrate that codelivering GFs with ECM-binding IL-1Ra induces superior regeneration. Thus, we highlight that GF regenerative activity is hindered by proinflammatory signals, and GF-based therapies should integrate immunomodulation. Particularly, ECM-binding IL-1Ra holds clinical translational potential by enhancing efficacy of GF therapies.

show abstract

Section: Discussionmentioning

confidence: 99%

Enhancing the regenerative effectiveness of growth factors by local inhibition of interleukin-1 receptor signaling

et al. 2020

View full text Add to dashboard Cite

show abstract

“…BMP-2 expression has been described in a plethora of macrophage subtypes, with M1 macrophages secreting particularly high levels of BMP-2 (50,51). BMP-2 is also involved in monocyte chemotaxis and cell adhesion, and prevents their differentiation into M2 macrophages, demonstrating its role in pro-inflammatory signaling (52). M2 macrophages stimulate mesenchymal stem cell proliferation and osteogenic differentiation through BMP-2 signaling (53).…”

Section: Discussionmentioning

confidence: 99%

Loss of Myeloid BMPR1a Alters Differentiation and Reduces Mouse Prostate Cancer Growth

et al. 2020

View full text Add to dashboard Cite

The Bone Morphogenetic Protein (BMP) pathway is a member of the TGFβ signaling family and has complex roles in cancer. BMP signaling is rarely mutated and can be frequently overexpressed in many human cancers. The dichotomous role of BMPs as both tumor promoters and suppressors appears to be largely context based in both the cancer cell and the surrounding microenvironment. Myeloid cells including macrophages and neutrophils have been shown to be tumor promoting when stimulated from BMPs. We found that conditional deletion of BMPR1a in myeloid cells (LysMCre) restricts tumor progression in a syngeneic mouse prostate cancer model. Specific changes occurred in myeloid cells both in tumor bearing mice and tumor naïve mice throughout multiple tissues. We profiled myeloid subsets in the bone marrow, spleen and primary tumor and found myeloid BMPR1a loss altered the differentiation and lineage capability of distinct populations by histologic, flow cytometry and high dimensional mass cytometry analysis. We further confirmed the requirement for BMP signaling with pharmacologic inhibition of THP-1 and Raw264.7 activated into M2 macrophages with the BMP inhibitor DMH1. M2 polarized primary bone marrow derived cells from LysMCre BMPR1a knockout mice indicated a distinct requirement for BMP signaling in myeloid cells during M2 activation. These results indicate a unique necessity for BMP signaling in myeloid cells during tumor progression.

show abstract

“…On the contrary, we found that the decreased serum level of sST2 on the first day after MI and serum levels of hCRP and MMP-9 on the third day after MI correlate with high serum BMP-4 levels, which may indicate that BMP-4 exhibits anti-inflammatory activity. In addition, BMP-2 is known to induce chemotaxis of monocytes and disrupt their differentiation into anti-inflammatory M2 macrophages [ 27 ]. Perhaps, this can explain the absence of significant dynamics of serum levels of BMP-4 with anti-inflammatory activity in the early period of AMI in our study.…”

Section: Discussionmentioning

confidence: 99%

Serum Levels of Bone Morphogenetic Proteins 2 and 4 in Patients with Acute Myocardial Infarction

Kercheva

Гусакова

Ryabova

et al. 2020

Cells

View full text Add to dashboard Cite

Background: Bone morphogenetic proteins-2 and -4 (BMPs) have been implicated in left ventricular remodeling (LVR) processes such as an inflammation and fibrogenesis. We hypothesized that this knowledge could be translated into clinics. Methods: We studied the dynamics of serum levels of BMPs, its correlation with markers of LVR and with parameters of echocardiography in patients (n = 31) during the six-month follow-up period after myocardial infarction (MI). Results: Elevated serum levels of BMPs decreased by the six-month follow-up period. BMP-2 decreased from the first day after MI, and BMP-4 decreased from the Day 14. The elevated level of BMP-2 at Day 1 was associated with a lower level of troponin I, reperfusion time and better left ventricular ejection fraction (LV EF) at the six-month follow-up. Elevated serum level of BMP-4 at Day 1 was associated with a lower level of a soluble isoform of suppression of tumorigenicity 2 (sST2), age and reperfusion time. An elevated level of BMP-2 at the six-month follow-up was associated with higher levels of BMP-4, high-sensitivity C-reactive protein (hCRP) and sST2. High serum level of BMP-2 correlated with high levels of hCRP and matrix metalloproteinase (MMP)-9 on Day 7. High serum level of BMP-4 correlated with low levels of hCRP, MMP-9 at Day 3, sST2 at Day 1 and with decreased LV EF on Day 7. The findings of multivariate analysis support the involvement of BMP-2 in the development of post-infarction LVR. Conclusions: Our research translates experimental data about the BMPs in the development of adverse LVR into the clinic. Elevated serum levels of BMPs decreased by the end of the six-month period after MI. BMP-2 decreased from the first day and BMP-4 decreased from Day 14. BMP-2 and BMP-4 were associated with the development of LVR. Their correlations with markers of inflammation, degradation of the extracellular matrix, hemodynamic stress and markers of myocardial damage further support our hypothesis. Diagnostic and predictive values of these BMPs at the development of post-infarction LVR in vivo should be investigated further.

show abstract

BMP‐2 induces human mononuclear cell chemotaxis and adhesion and modulates monocyte‐to‐macrophage differentiation

Cited by 28 publications

References 42 publications

Enhancing the regenerative effectiveness of growth factors by local inhibition of interleukin-1 receptor signaling

Enhancing the regenerative effectiveness of growth factors by local inhibition of interleukin-1 receptor signaling

Loss of Myeloid BMPR1a Alters Differentiation and Reduces Mouse Prostate Cancer Growth

Serum Levels of Bone Morphogenetic Proteins 2 and 4 in Patients with Acute Myocardial Infarction

Contact Info

Product

Resources

About