Acute phase serum amyloid A induces proinflammatory cytokines and mineralization via toll-like receptor 4 in mesenchymal stem cells

Ebert, Regina; Benisch, Peggy; Krug, Melanie; Zeck, Sabine; Meissner‐Weigl, Jutta; Steinert, Andre F.; Rauner, Martina; Hofbauer, Lorenz C.; Jakob, Franz

doi:10.1016/j.scr.2015.06.008

Cited by 53 publications

(53 citation statements)

References 45 publications

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“…In a recent study by Ebert et al . 46 , SAA1 was shown to stimulate a pro-inflammatory phenotype via TLR4 in mesenchymal stem cells by activation of p38 and NFκB pathways, which was believed to be part of the early phase of osteogenic differentiation and the development of senescence. Here we demonstrated that similar signaling pathways underpinned the actions of SAA1 in human amnion fibroblasts.…”

Section: Discussionmentioning

confidence: 99%

Induction of pro-inflammatory genes by serum amyloid A1 in human amnion fibroblasts

Wang

Zuo

et al. 2017

Sci Rep

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Serum amyloid A1 (SAA1) is an acute response protein, which is mainly produced by the liver, during infection. However, it remains unknown whether SAA1 can be produced in human fetal membranes where it is able to elicit events pertinent to labor initiation. We demonstrated that SAA1 was expressed in the fibroblasts and epithelium of the amnion and the trophoblasts of the chorion. Further study in human amnion fibroblasts showed that SAA1 production was augmented by interleukin-1β (IL-1β) and cortisol alone and synergistically, and SAA1 in turn induced the expression of IL-1β, interleukin-6 (IL-6), cyclooxygenase-2 (COX-2) and PGE2 production. These effects of SAA1 were mediated through activation of the NF-κB, p38 and ERK1/2 pathways via the toll-like receptor 4 (TLR4). Inhibition of TLR4 attenuated not only SAA1-induced activation of NF-κB, p38 and ERK1/2 but also increases in IL-1β, IL-6 and COX-2 expression. Moreover, SAA1 expression was increased in human amnion tissue following spontaneous labor. In conclusion, this study has demonstrated for the first time that SAA1 can be produced in human fetal membranes, which can be greatly induced in the presence of proinflammatory cytokines and glucocorticoids thereby producing effects associated with parturition.

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Section: Discussionmentioning

confidence: 99%

Induction of pro-inflammatory genes by serum amyloid A1 in human amnion fibroblasts

Wang

Zuo

et al. 2017

Sci Rep

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“…A list of genes (selected by the authors using educated guesses) that are upregulated after respective time points is provided in Table 1; complete lists can be found in the article. Interestingly, the early genes such as proinflammatory cytokines IL-1b, IL-6, IL-8, the toll-like receptor 4 (TLR4) ligands serum amyloid A1 (SAA1) and SAA2, CYR61/CCN1, connective tissue growth factor (CTGF/CCN2), angiopoietin-like 4 (ANGPTL4) and ANGPTL2 very closely resemble genes that are also relevant in the initial phase of osteogenic differentiation and contribute to angiogenesis in fracture healing [91][92][93]. Already after 2h, the mRNAs encoding proinflammatory genes have gone back to basal levels.…”

Section: Muscle Secretory Products With Endocrine Functionsmentioning

confidence: 99%

“…Many of these genes have putative functions in bone regeneration (see also text). Virtually all genes of the inflammatory phase have implications in the early phase of skeletal stem cell commitment and bone regeneration; also, genes active in neoangiogenesis are relevant for bone healing, regeneration, and remodeling [82,91,96,97]. Abbreviations: CYR61/CCN1: cysteine-rich angiogenic inducer 61, TNF: tumor necrosis factor.…”

Section: Muscle Secretory Products With Endocrine Functionsmentioning

confidence: 99%

“…It is supported by a proinflammatory reaction initiated by platelets in case of injury (platelet-derived growth factor (PDGF) and cytokine signaling) and/or by TLR 2 and 4 and their ligands such as SAA1 and SAA2 or cell fragments and DNA. This initiates a cascade of cytokines involving e.g., IL-1, IL-6, IL-8, and other proinflammatory polypeptides as well as Wnt5A as part of the non-canonical osteogenic Wnt pathway (see also Table 1 for their involvement in muscle regeneration) [91,[122][123][124]. Not only is this condition in common for regenerating tissues in the early phase, but it also somehow mimics the senescence-associated secretory phenotype (SASP) of presenescent and senescent cells.…”

Section: Principles Of Bone Formation Maintenance and Regenerationmentioning

confidence: 99%

“…This form of inflammation can seriously impair tissue regeneration on several levels and in several segments. While inflammation is an essential part of the initial phase of tissue regeneration, the failure of timely resolution through anti-inflammatory cytokines is key for these roadblocks and it also drives aging and the manifestations of an inflammatory senescence-associated phenotype (SASP) [91,[107][108][109]177]. Inflammation and disuse also propagate muscle fatty infiltration and bone marrow adipose expansion, which even more contributes to inflammatory activity initiating a vicious cycle.…”

Section: Inflammation and Fatty Degeneration-lessons From Imaging Andmentioning

confidence: 99%

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Interactions between Muscle and Bone—Where Physics Meets Biology

et al. 2020

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Muscle and bone interact via physical forces and secreted osteokines and myokines. Physical forces are generated through gravity, locomotion, exercise, and external devices. Cells sense mechanical strain via adhesion molecules and translate it into biochemical responses, modulating the basic mechanisms of cellular biology such as lineage commitment, tissue formation, and maturation. This may result in the initiation of bone formation, muscle hypertrophy, and the enhanced production of extracellular matrix constituents, adhesion molecules, and cytoskeletal elements. Bone and muscle mass, resistance to strain, and the stiffness of matrix, cells, and tissues are enhanced, influencing fracture resistance and muscle power. This propagates a dynamic and continuous reciprocity of physicochemical interaction. Secreted growth and differentiation factors are important effectors of mutual interaction. The acute effects of exercise induce the secretion of exosomes with cargo molecules that are capable of mediating the endocrine effects between muscle, bone, and the organism. Long-term changes induce adaptations of the respective tissue secretome that maintain adequate homeostatic conditions. Lessons from unloading, microgravity, and disuse teach us that gratuitous tissue is removed or reorganized while immobility and inflammation trigger muscle and bone marrow fatty infiltration and propagate degenerative diseases such as sarcopenia and osteoporosis. Ongoing research will certainly find new therapeutic targets for prevention and treatment.

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Physical contact between mesenchymal stem cells and endothelial precursors induces distinct signatures with relevance to the very early phase of regeneration

Hafen

Wiesner

Schlegelmilch

et al. 2018

J of Cellular Biochemistry

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Multipotent adult stem cells/precursor cells, especially of the mesenchymal and endothelial lineage, may have great potential for bone tissue engineering. Although their potential is highly recognized, not much is known about the underlying molecular mechanisms that initiate the regeneration process, connect osteogenesis, and angiogenesis and, finally, orchestrate renewal of bone tissue. Our study addressed these questions by generating two in vitro cell culture models to examine the changes in the global gene expression patterns of endothelial precursor cells and mesenchymal stem cells after 24 hours of either humoral (conditioned medium) or direct cell-cell interaction (co-culture). Endothelial precursor cells were isolated from human buffy coat and mesenchymal stem cells from the bone marrow of the femoral head. The comparison of the treated and control cells by microarray analyses revealed in total more than 1500 regulated genes, which were analyzed for their affiliation to angiogenesis and osteogenesis. Expression array analyses at the RNA and protein level revealed data with respect to regulated genes, pathways and targets that may represent a valid basis for further dissection of the systems biology of regeneration processes. It may also be helpful for the reconstitution of the natural composition of a regenerative microenvironment when targeting tissue regeneration both in vitro and in situ.

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Acute phase serum amyloid A induces proinflammatory cytokines and mineralization via toll-like receptor 4 in mesenchymal stem cells

Cited by 53 publications

References 45 publications

Induction of pro-inflammatory genes by serum amyloid A1 in human amnion fibroblasts

Induction of pro-inflammatory genes by serum amyloid A1 in human amnion fibroblasts

Interactions between Muscle and Bone—Where Physics Meets Biology

Physical contact between mesenchymal stem cells and endothelial precursors induces distinct signatures with relevance to the very early phase of regeneration

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