scholarly journals The Role of Tryptophan Metabolites in Musculoskeletal Stem Cell Aging

2020 ◽  
Vol 21 (18) ◽  
pp. 6670
Author(s):  
Jordan Marcano Anaya ◽  
Wendy B. Bollag ◽  
Mark W. Hamrick ◽  
Carlos M. Isales

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.

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A279-A280
Author(s):  
Maria Chang Villacreses ◽  
Panadeekarn Panjawatanan ◽  
Rudruidee Karnchanasorn ◽  
Horng-Yih Ou ◽  
Wei Feng ◽  
...  

Abstract It is generally acknowledged that fracture rate is higher in diabetic subjects than non-diabetic subjects. However, the impact of diabetes on bone is less clear due to contradictory results of bone mineral density (BMD) and fracture rate. To date, most of reports were based on the studies from relatively small sample sizes. To clarify the issues, we examined the fracture rates and BMD across a spectrum of glucose tolerance in a representative US population. The participants of the National Health and Nutrition Survey 2005–2010 were used in this study. Among adult subjects (age≥20 years old) with reported BMI, we were able to define the states of glucose tolerance in 31,073 subjects cording to the diagnostic criteria based on HbA1c, fasting glucose, and/or 2-h post-changed glucose with established diabetes and using diabetes medications, into normal glucose tolerance (NGT), abnormal glucose tolerance (AGT), and diabetes mellitus (DM). Those who received osteoporosis medications were excluded from BMD analysis. Fracture information was available in 15,547 subjects; validated hip BMD was available in 12,317 subjects; and validated lumbar spine BMD was available in 10,329 subjects. Fracture rates were compared among 3 groups of glucose tolerance states and odds ratio (OR) with 95% confidence intervals (95% CI) were calculated in reference to the NGT group with sample weighting. BMD was compared among 3 groups of glucose tolerance with consideration of covariates. The reported osteoporosis diagnosed rate differed among 3 groups of glucose tolerances (3.99%, 5.77%, and 8.41%, P<0.001, for NGT, AGT, and DM respectively). Worsening states of glucose tolerance were associated increased fracture OR at Hip [AGT, 2.1770 (95% CI: 2.1732–2.1807) and DM, 2.7369 (95% CI: 2.7315–2.7423)], spine [AGT, 0.9924 (95% CI: 0.9912–0.9936); DM, 1.2405 (95% CI: 1.2387–1.2423)]. In contrast, a different trend was observed on the wrist fracture rate [AGT, 0.9556 (95% CI: 0.9551–0.9562); DM, 0.9053 (95% CI: 0.9045–0.9060)]. After adjustment for covariates, higher BMD was noted in AGT and DM when compared to NGT at total femur (NGT, 0.9760±0.0015 gm/cm2; AGT, 0.9853±0.0021 gm/cm2; DM 0.9847±0.0034 gm/cm2, mean±SE, P=0.001) and femoral neck (NGT, 0.8388±0.0015 gm/cm2; AGT, 0.8474±0.0020 gm/cm2; DM, 0.8496±0.0032 gm/cm2, P=0.0007) while no difference was found in lumbar spine BMD (NGT, 0.1.0441±0.0018 gm/cm2; AGT, 1.0406±0.0025 gm/cm2; DM, 1.0464±0.0041 gm/cm2, P=0.35). Our observed significant increased fracture risk at hip (OR: 2.7369) and lumbar spine (OR: 1.2405) in DM subjects when compared to NGT subjects. DM subjects had higher BMD at total femur and femoral neck than NGT subjects while no difference was noted at lumbar spine BMD when compared to NGT subjects. Further studies are required to explore the discrepancy between the increased fracture risk with higher BMDs in diabetes.


2017 ◽  
Vol 19 (9) ◽  
Author(s):  
Joshua I. Barzilay ◽  
Barry R. Davis ◽  
Sara L. Pressel ◽  
Alokananda Ghosh ◽  
Rachel Puttnam ◽  
...  

2013 ◽  
Author(s):  
Julie Pasco ◽  
Stephen Lane ◽  
Sharon Brennan ◽  
Elizabeth Timney ◽  
Gosia Bucki-Smith ◽  
...  

Author(s):  
MINAKSHI JOSHI ◽  
SHRADHA BISHT ◽  
MAMTA F. SINGH

Thyroid hormone serves as an indispensable component for the optimum functioning of various biological systems. They curb body’s metabolism, regulates the estrogen level, regulates bone turnover, essential for skeletal development and mineralization. Within the scope of knowledge, it is intimately familiar that thyroid disorders have widespread systemic manifestations, among which in hypothyroidism, even though elevated TSH (thyroid-stimulating hormone) may reduce estrogen level which in turn stimulates osteoclasts and thus cause osteoporosis, while hyperthyroidism accelerates bone turnover. Hypothyroidism does not directly interfere with the skeletal integrity, but treatment with levothyroxine for the suppression of TSH to bring the hypothyroid patient to euthyroid state for a long haul; lead to simultaneous reduction in bone mass and in (bone mineral density) BMD. After the initial relevation of the correlation between thyroid disorders and osteoporosis in numerous studies have emphasized that both hypo and hyperthyroidism either directly or indirectly affects the bone mineral density or leads to the progression of osteoporosis. Therefore the present study is aimed and so designed to review all the possible associations between them and the impact of thyroid disorders on estrogen level and bone mineral density. The main findings of this review indicate that both excesses as well as deficiency of thyroid hormone can be potentially deleterious for bone tissue.


Sign in / Sign up

Export Citation Format

Share Document