GDF11 Inhibits Bone Formation by Activating Smad2/3 in Bone Marrow Mesenchymal Stem Cells

Lu, Qiong; Tu, Manli; Li, Changjun; Zhang, Li; Tong, Jiang; Liu, Tang; Luo, Xi

doi:10.1007/s00223-016-0173-z

Cited by 37 publications

(36 citation statements)

References 30 publications

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“…In contrast, growth differentiation factor GDF11/BMP11 has been identified as a rejuvenating factor for neuronal tissue, vasculature, cardiac and skeletal muscle; however, due to the high similarity of GDF11 to myostatin/GDF8, there are doubts about the specificity of these data [21]. Adding to this controversy and enforcing the earlier notion that a general increase in TGF-β/BMP signaling is detrimental, GDF11 has been shown to accelerate age-related bone loss in mice [22]. …”

Section: Mammalian Epimorphic Regeneration: Major Steps and The Impacmentioning

confidence: 77%

The Impact of Aging on Mechanisms of Mammalian Epimorphic Regeneration

Brunauer

Muneoka²

2018

Gerontology

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Aging is associated with a significant decline of tissue repair and regeneration, ultimately resulting in tissue dysfunction, multimorbidity, and death. Salamanders possess remarkable regenerative abilities and have been studied with the prospect of inducing regeneration in humans and counteracting regenerative decline with aging. However, epimorphic regeneration, the full replacement of amputated structures, also occurs in mammals. One of the best studied models is digit tip regeneration, which is described for mice, and occurs in humans in a comparable manner. To accomplish regeneration, the amputated digit tip has to undergo three interdependent, overlapping steps: (i) wound healing without formation of a scar; (ii) formation of a blastema, a highly proliferative cell mass; and (iii) spatiotemporally regulated differentiation to generate a pattern similar to the original structure. Aging likely interferes with each of these steps. In this article, we provide an overview of the critical signaling pathways for regeneration, as revealed by investigating mammalian digit regeneration, the possible impact of aging on these pathways, and approaches to induce regeneration in the elderly. We hypothesize that with aging, increased Wnt signaling, NF-κB and tumor suppressor activity, and loss of positional information hampers regeneration. Knowledge about the impact of aging on regenerative mechanisms will enable us to safely activate endogenous regeneration in the elderly, and to generate a regeneration-permissive environment for cell therapies.

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Section: Mammalian Epimorphic Regeneration: Major Steps and The Impacmentioning

confidence: 77%

The Impact of Aging on Mechanisms of Mammalian Epimorphic Regeneration

Brunauer

Muneoka²

2018

Gerontology

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“…This concept, however, has been challenged by the findings of several different labs [88–90]. Most recently, it was shown that overexpression of GDF11 in mice induces muscle atrophy, inhibits skeletal muscle regeneration, leads to bone loss, and blocks bone resorption; all outcomes that argue that increasing GDF11 would not be a beneficial strategy for musculoskeletal health [73, 89, 91, 92]. We found that the average expression of Gdf11 decreases approximately 17% in iMS Bmal1 −/− mice 5 weeks post knockout of Bmal1 .…”

Section: The Effect Of Bmal1 Knockout In Muscle On Bonementioning

confidence: 99%

The Role of the Molecular Clock in Skeletal Muscle and What It Is Teaching Us About Muscle-Bone Crosstalk

Riley

Esser

2017

Curr Osteoporos Rep

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Purpose of ReviewThis review summarizes what has been learned about the interaction between skeletal muscle and bone from mouse models in which BMAL1, a core molecular clock protein has been deleted. Additionally, we highlight several genes which change following loss of BMAL1. The protein products from these genes are secreted from muscle and have a known effect on bone homeostasis.Recent FindingsCircadian rhythms have been implicated in regulating systems homeostasis through a series of transcriptional-translational feedback loops termed the molecular clock. Recently, skeletal muscle-specific disruption of the molecular clock has been shown to disrupt skeletal muscle metabolism. Additionally, loss of circadian rhythms only in adult muscle has an effect on other tissue systems including bone.SummaryOur finding that the expression of a subset of skeletal muscle-secreted proteins changes following BMAL1 knockout combined with the current knowledge of muscle-bone crosstalk suggests that skeletal muscle circadian rhythms are important for maintenance of musculoskeletal homeostasis. Future research on this topic may be important for understanding the role of the skeletal muscle molecular clock in a number of diseases such as sarcopenia and osteoporosis.

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“…bone formation and induces bone loss in mice. 18 The results of in vivo studies, which may more accurately reflect actual conditions, have demonstrated that GDF11 inhibits bone formation. [18][19][20] The GDF11 amino acid sequence is 90% identical to that of myostatin (GDF8).…”

Section: Recent Data Show That Intraperitoneal Injection Of Gdf11 Inhmentioning

confidence: 99%

“…18 The results of in vivo studies, which may more accurately reflect actual conditions, have demonstrated that GDF11 inhibits bone formation. [18][19][20] The GDF11 amino acid sequence is 90% identical to that of myostatin (GDF8). [21][22][23] Previous studies have documented that mice with myostatin deficiency present increased osteogenic differentiation and bone mass compared to wild-type mice.…”

Section: Recent Data Show That Intraperitoneal Injection Of Gdf11 Inhmentioning

confidence: 99%

Increased serum GDF11 concentration is associated with a high prevalence of osteoporosis in elderly native Chinese women

Jin

Song

Guo

et al. 2016

Clin Exp Pharma Physio

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Osteoporosis is an age-related disease. Many studies have confirmed the anti-aging effect of growth differentiation factor 11 (GDF11), but the action of GDF11 on bone metabolism remains unclear. In this study, we aimed to investigate the relationship between serum GDF11 levels and the prevalence of osteoporosis. Our data indicate negative correlations between serum GDF11 levels and BMD at the lumbar spine and femoral neck. The serum GDF11 levels were grouped into quartile intervals, and the prevalence and risk of osteoporosis were found be markedly greater with increased GDF11 levels. This study demonstrated that GDF11 was negatively correlated with BMD in elderly Chinese women. Furthermore, osteoporotic risk was significantly increased with increases in GDF11 levels.

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GDF11 Inhibits Bone Formation by Activating Smad2/3 in Bone Marrow Mesenchymal Stem Cells

Cited by 37 publications

References 30 publications

The Impact of Aging on Mechanisms of Mammalian Epimorphic Regeneration

The Impact of Aging on Mechanisms of Mammalian Epimorphic Regeneration

The Role of the Molecular Clock in Skeletal Muscle and What It Is Teaching Us About Muscle-Bone Crosstalk

Increased serum GDF11 concentration is associated with a high prevalence of osteoporosis in elderly native Chinese women

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