Age-related increase of kynurenine enhances miR29b-1-5p to decrease both CXCL12 signaling and the epigenetic enzyme Hdac3 in bone marrow stromal cells

Elmansi, Ahmed M.; Hussein, Khaled A.; Mas, Sergi; Periyasamy‐Thandavan, Sudharsan; Aguilar-Pérez, Alexandra; Kondrikova, Galina; Kondrikov, Dmitry; Eisa, Nada H.; Pierce, Jessica L.; Kaiser, Helen; Ding, Ke; Walker, Aisha L.; Jiang, Xue; Bollag, Wendy B.; Elsalanty, Mohammed; Zhong, Qing; Shi, Xing Ming; Su, Yun; Johnson, Maribeth H.; Hunter, Monte; Reitman, Charles A.; Volkman, Brian F.; Hamrick, Mark W.; Isales, Carlos M.; Fulzele, Sadanand; McGee‐Lawrence, Meghan E.; Hill, William

doi:10.1016/j.bonr.2020.100270

Cited by 22 publications

(11 citation statements)

References 112 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently, a number of studies have focused on the potential mechanisms through which Kyn could induce an aging phenotype in bone. These include: enhanced MSC senescence, decreased autophagy, increased oxidative stress, reduced osteogenic factors, and altered miRNA expression, among others [23][24][25]. Although much of the bone-related research focuses on Kyn, not much is known about other Trp metabolites, specifically those downstream of Kyn.…”

Section: Kynurenine Impacts Mscs and Causes Age-related Bone Lossmentioning

confidence: 99%

The Role of Tryptophan Metabolites in Musculoskeletal Stem Cell Aging

Anaya

Bollag

Hamrick

et al. 2020

IJMS

Self Cite

View full text Add to dashboard Cite

Although aging is considered a normal process, there are cellular and molecular changes that occur with aging that may be detrimental to health. Osteoporosis is one of the most common age-related degenerative diseases, and its progression correlates with aging and decreased capacity for stem cell differentiation and proliferation in both men and women. Tryptophan metabolism through the kynurenine pathway appears to be a key factor in promoting bone-aging phenotypes, promoting bone breakdown and interfering with stem cell function and osteogenesis; however, little data is available on the impact of tryptophan metabolites downstream of kynurenine. Here we review available data on the impact of these tryptophan breakdown products on the body in general and, when available, the existing evidence of their impact on bone. A number of tryptophan metabolites (e.g., 3-hydroxykynurenine (3HKYN), kynurenic acid (KYNA) and anthranilic acid (AA)) have a detrimental effect on bone, decreasing bone mineral density (BMD) and increasing fracture risk. Other metabolites (e.g., 3-hydroxyAA, xanthurenic acid (XA), picolinic acid (PIA), quinolinic acid (QA), and NAD+) promote an increase in bone mineral density and are associated with lower fracture risk. Furthermore, the effects of other tryptophan breakdown products (e.g., serotonin) are complex, with either anabolic or catabolic actions on bone depending on their source. The mechanisms involved in the cellular actions of these tryptophan metabolites on bone are not yet fully known and will require further research as they are potential therapeutic targets. The current review is meant as a brief overview of existing English language literature on tryptophan and its metabolites and their effects on stem cells and musculoskeletal systems. The search terms used for a Medline database search were: kynurenine, mesenchymal stem cells, bone loss, tryptophan metabolism, aging, and oxidative stress.

show abstract

Section: Kynurenine Impacts Mscs and Causes Age-related Bone Lossmentioning

confidence: 99%

The Role of Tryptophan Metabolites in Musculoskeletal Stem Cell Aging

Anaya

Bollag

Hamrick

et al. 2020

IJMS

Self Cite

View full text Add to dashboard Cite

show abstract

“…With the growing evidence of the important regulatory roles of miRNAs in aged osteoblast differentiation and aging-related bone loss 7 - 9 , 25 , 30 - 34 , the relationship between miRNAs and senile osteoporosis has become a focus of substantial research. Recently, miR-146a was found to be an essential epigenetic switch controlling osteoblast generation and aging-related bone loss by regulating bone anabolic Wnt signaling 25 .…”

Section: Discussionmentioning

confidence: 99%

MiR-138-5p Targets MACF1 to Aggravate Aging-related Bone Loss

Chen¹,

Huai²,

Chen³

et al. 2022

Int. J. Biol. Sci.

View full text Add to dashboard Cite

“…Functioning as a transcription factor, this complex can upregulate miR-29B-1-5p expression and downregulate that of HDAC3 and CXCL12, thus shifting BMSC differentiation from osteogenic to adipogenic fates. 213,214 5-HT is an important neurotransmitter that does not cross the blood-brain barrier and can be divided into central and peripheral 5-HT based on its origins. More than 95% of this neurotransmitter originates in the gut and is associated with the activity of tryptophan 5-hydroxylase 1 (TPH1), the ratelimiting enzyme in serotonin biosynthesis in enterochromaffin cells (ECs).…”

Section: Aromatic Amino Acidsmentioning

confidence: 99%

“…Furthermore, following Kyn/AHR binding in the cytoplasm of BMSCs, the complex is transported into the nucleus where it binds to aryl hydrocarbon receptor nuclear transposer (ARNT). Functioning as a transcription factor, this complex can upregulate miR‐29B‐1‐5p expression and downregulate that of HDAC3 and CXCL12, thus shifting BMSC differentiation from osteogenic to adipogenic fates 213,214 …”

Section: Gm‐derived Metabolites and Bone Metabolismmentioning

confidence: 99%

Gut microbiota and bone metabolism

Chen

Liu

et al. 2021

The FASEB Journal

View full text Add to dashboard Cite

Osteoporosis is the most common metabolic skeletal disease. It is characterized by the deterioration of the skeletal microarchitecture and bone loss, leading to ostealgia, and even bone fractures. Accumulating evidence has indicated that there is an inextricable relationship between the gut microbiota (GM) and bone homeostasis involving host–microbiota crosstalk. Any perturbation of the GM can play an initiating and reinforcing role in disrupting the bone remodeling balance during the development of osteoporosis. Although the GM is known to influence bone metabolism, the mechanisms associated with these effects remain unclear. Herein, we review the current knowledge of how the GM affects bone metabolism in health and disease, summarize the correlation between pathogen‐associated molecular patterns of GM structural components and bone metabolism, and discuss the potential mechanisms underlying how GM metabolites regulate bone turnover. Deciphering the complicated relationship between the GM and bone health will provide new insights into the prevention and treatment of osteoporosis.

show abstract

Age-related increase of kynurenine enhances miR29b-1-5p to decrease both CXCL12 signaling and the epigenetic enzyme Hdac3 in bone marrow stromal cells

Cited by 22 publications

References 112 publications

The Role of Tryptophan Metabolites in Musculoskeletal Stem Cell Aging

The Role of Tryptophan Metabolites in Musculoskeletal Stem Cell Aging

MiR-138-5p Targets MACF1 to Aggravate Aging-related Bone Loss

Gut microbiota and bone metabolism

Contact Info

Product

Resources

About