Transforming Growth Factor-β Promotes Recruitment of Bone Marrow Cells and Bone Marrow-derived Mesenchymal Stem Cells through Stimulation of MCP-1 Production in Vascular Smooth Muscle Cells

Zhang, Fan; Tsai, Shirling; Kato, Kaori; Yamanouchi, Dai; Wang, Chunjie; Rafii, Shahin; Liu, Bo; Kent, K. Craig

doi:10.1074/jbc.m109.013987

Cited by 114 publications

(94 citation statements)

References 48 publications

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“…To examine the changes at the disease has drawn increasing attention in recent years. During tissue injury or remodeling, TGF-β is activated to recruit stem/ progenitor cells to maintain tissue homeostasis (27)(28)(29)(30)(31). We have previously shown that TGF-β is released from the bone matrix and activated during osteoclastic bone resorption (31).…”

Section: Resultsmentioning

confidence: 99%

Aberrant TGF-β activation in bone tendon insertion induces enthesopathy-like disease

Wang¹,

Xie²,

Crane³

et al. 2018

Journal of Clinical Investigation

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and systemically in spondyloarthropathy patients with enthesopathy (37,38). In this study, we determined the role of TGF-β in Achilles tendon enthesopathy using 3 different mouse models. We found that the changes of calcaneal bone microstructure and composition were associated with the onset of Achilles tendon enthesopathy. Inhibition of TGF-β activity, using either a TGF-β-neutralizing antibody (1D11) or a conditional knockout mouse model, attenuated calcaneal and fibrocartilage pathological changes. ResultsUpregulated TGF-β activities in posterior calcaneal tuberosity in Achilles tendon enthesopathy mouse models. To examine the changes at the disease has drawn increasing attention in recent years. During tissue injury or remodeling, TGF-β is activated to recruit stem/ progenitor cells to maintain tissue homeostasis (27)(28)(29)(30)(31). We have previously shown that TGF-β is released from the bone matrix and activated during osteoclastic bone resorption (31). Active TGF-β induces mesenchymal stromal stem cell (MSC) migration to the bone-resorptive pits for new bone formation (31). However, excessive active TGF-β leads to uncoupled bone remodeling, contributing to the pathogenesis of rare genetic skeletal diseases such as Camurati-Engelmann disease (CED), osteogenesis imperfecta, and more common musculoskeletal disorders, such as osteoarthritis (31-36). High levels of TGF-β have been observed locally lower in relation to sham-operated controls ( Figure 1B). Moreover, a dramatically higher trabecular pattern factor (Tb.Pf), a quantitative parameter of the connectiveness and microarchitecture of trabecular bone (40), was noted in the SMTS mice compared with sham-operated controls, indicating uncoupled bone remodeling ( Figure 1B). Evident bony projections at the PCT were present in 4 of 10 mice 8 weeks after SMTS ( Figure 1A). The BV/TV, Tb.N, and Tb.Th of vertebral bodies were not significantly changed in the SMTS group compared with controls at week 8 (Supplemental Figure 2). Tartrate-resistant acid phosphatase (TRAP) staining showed that the osteoclast surface per bone surface (OCS/BS) increased in PCT trabecular bone 1 and 2 weeks after surgery and was back to normal levels on week 4 after surgery (Figure 1, C and D) while leaving large bone marrow cavities ( Figure 1C). A significantly higher active TGF-β concentration in serum was seen in the SMTS mice relative to sham-operated mice from 1 to 8 weeks after onset of enthesopathy, we generated these 2 models based on prior theories that enthesopathy results from unbalanced mechanical loading (2, 39). The first model we generated decreased mechanical load by partially transecting Achilles tendons in the middle of tendon body in 3-month-old male mice, termed semi-Achilles tendon transection (SMTS) (Supplemental Figure 1; supplemental material available online with this article; https://doi.org/10.1172/ JCI96186DS1). The bone volume over total tissue volume (BV/ TV) in the posterior calcaneal tuberosity (PCT), the site of Achilles tendon attachment to calcane...

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Section: Resultsmentioning

confidence: 99%

Aberrant TGF-β activation in bone tendon insertion induces enthesopathy-like disease

Wang¹,

Xie²,

Crane³

et al. 2018

Journal of Clinical Investigation

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“…2D). Thus, although TGFb1 does not directly enhance the ability of monocytes to produce angiogenic factors, it may enhance the proangiogenic environment by increasing the number of infiltrating monocytes, a similar phenomenon as that described for smooth muscle cells (22,23).…”

Section: Tgfb1 Enhances Mcp-1-mediated Monocyte Migrationmentioning

confidence: 96%

Induction of Monocyte Chemoattractant Protein-1 and Interleukin-10 by TGFβ1 in Melanoma Enhances Tumor Infiltration and Immunosuppression

et al. 2011

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Melanoma progression is associated with the expression of different growth factors, cytokines, and chemokines. Because TGFb1 is a pleiotropic cytokine involved not only in physiologic processes but also in cancer development, we analyzed in A375 human melanoma cells, the effect of TGFb1 on monocyte chemoattractant protein-1 (MCP-1) and interleukin-10 (IL-10) expression, two known factors responsible for melanoma progression. TGFb1 increased the expression of MCP-1 and IL-10 in A375 cells, an effect mediated by the cross-talk between Smad, PI3K (phosphoinositide 3-kinase)/AKT, and BRAF-MAPK (mitogen activated protein kinase) signaling pathways. Supernatants from TGFb1-treated A375 cells enhanced MCP-1-dependent migration of monocytes, which, in turn, expressed high levels of TGF,b1, bFGF, and VEGF mRNA. Moreover, these supernatants also inhibited functional properties of dendritic cells through IL-10-dependent mechanisms. When using in vitro, the TGFb1-blocking peptide P144, TGFb1-dependent Smad3 phosphorylation, and expression of MCP-1 and IL-10 were inhibited. In vivo, treatment of A375 tumor-bearing athymic mice with P144 significantly reduced tumor growth, associated with a lower macrophage infiltrate and decreased intratumor MCP-1 and VEGF levels, as well as angiogenesis. Finally, in C57BL/6 mice with B16-OVA melanoma tumors, when administered with immunotherapy, P144 decreased tumor growth and intratumor IL-10 levels, linked to enhanced activation of dendritic cells and natural killer cells, as well as anti-OVA T-cell responses. These results show new effects of TGFb1 on melanoma cells, which promote tumor progression and immunosuppression, strongly reinforcing the relevance of this cytokine as a molecular target in melanoma.

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“…Indeed, TGF-b is known to induce IL-6 and/or MCP-1 expression in many cell types, including fibroblasts and vascular smooth muscle cells (31)(32)(33)(34)(35) and to induce innate immune responses, including monocyte recruitment and macrophage differentiation. These events can stimulate myofibroblast formation from fibroblasts or endothelial cells (EnMT), which in turn may amplify the process through secretion of TGF-b, MMPs, or even MCP-1 (36, 37) in some tissues.…”

Section: Tgf-β and Models Of Abdominal Aortic Aneurysmmentioning

confidence: 99%

TGF-β in the pathogenesis and prevention of disease: a matter of aneurysmic proportions

Dietz¹

2010

J. Clin. Invest.

108

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Transforming Growth Factor-β Promotes Recruitment of Bone Marrow Cells and Bone Marrow-derived Mesenchymal Stem Cells through Stimulation of MCP-1 Production in Vascular Smooth Muscle Cells

Cited by 114 publications

References 48 publications

Aberrant TGF-β activation in bone tendon insertion induces enthesopathy-like disease

Aberrant TGF-β activation in bone tendon insertion induces enthesopathy-like disease

Induction of Monocyte Chemoattractant Protein-1 and Interleukin-10 by TGFβ1 in Melanoma Enhances Tumor Infiltration and Immunosuppression

TGF-β in the pathogenesis and prevention of disease: a matter of aneurysmic proportions

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