scholarly journals Bone Biomarkers in Mucopolysaccharidoses

2021 ◽  
Vol 22 (23) ◽  
pp. 12651
Author(s):  
Akari Nakamura-Utsunomiya

The accumulation of glycosaminoglycans (GAGs) in bone and cartilage leads to progressive damage in cartilage that, in turn, reduces bone growth by the destruction of the growth plate, incomplete ossification, and growth imbalance. The mechanisms of pathophysiology related to bone metabolism in mucopolysaccharidoses (MPS) include impaired chondrocyte function and the failure of endochondral ossification, which leads to the release of inflammatory cytokines via the activation of Toll-like receptors by GAGs. Although improvements in the daily living of patients with MPS have been achieved with enzyme replacement, treatment for the bone disorder is limited. There is an increasing need to identify biomarkers related to bone and cartilage to evaluate the progressive status and to monitor the treatment of MPS. Recently, new analysis methods, such as proteomic analysis, have identified new biomarkers in MPS. This review summarizes advances in clinical bone metabolism and bone biomarkers.

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Yu-Ting Yen ◽  
May Chien ◽  
Pei-Yi Wu ◽  
Shih-Chieh Hung

AbstractIt has not been well studied which cells and related mechanisms contribute to endochondral ossification. Here, we fate mapped the leptin receptor-expressing (LepR+) mesenchymal stem cells (MSCs) in different embryonic and adult extremities using Lepr-cre; tdTomato mice and investigated the underling mechanism using Lepr-cre; Ppp2r1afl/fl mice. Tomato+ cells appear in the primary and secondary ossification centers and express the hypertrophic markers. Ppp2r1a deletion in LepR+ MSCs reduces the expression of Runx2, Osterix, alkaline phosphatase, collagen X, and MMP13, but increases that of the mature adipocyte marker perilipin, thereby reducing trabecular bone density and enhancing fat content. Mechanistically, PP2A dephosphorylates Runx2 and BRD4, thereby playing a major role in positively and negatively regulating osteogenesis and adipogenesis, respectively. Our data identify LepR+ MSC as the cell origin of endochondral ossification during embryonic and postnatal bone growth and suggest that PP2A is a therapeutic target in the treatment of dysregulated bone formation.


PRILOZI ◽  
2017 ◽  
Vol 38 (1) ◽  
pp. 119-123
Author(s):  
Zoran Gucev ◽  
Velibor Tasic ◽  
Momir Polenakovic

Abstract The fifth SEE meeting on rare diseases (RDs) was held in Macedonian Academy of Sciences and Arts (MASA) the November 11th, 2016. Several lectures dealt with mucopolysaccharidosis, glycogen storage diseases and the possibilities for their diagnosis and treatment. Enzyme replacement treatment (ERT), its availability, effects (or the lack of it) on the brain, and further prospects of eventual gene treatment were comprehensively exposed and discussed. Special accent was on Gaucher, Morquio IVA, Hunter and the audience was given new knowledge on the complexities of diagnosis and treatment. A block of lectures on rare renal diseases was also impressive. From renal stones, their molecular and genetic mechanisms to different forms of CAKUT the use of NGS and other molecular methods in diagnosis of RDs. Mitochondrial diseases, the novelties and importance of early discovery were comprehensively exposed. Special lecture was given on the complement system. Endocrine disruptors, microprolactinomas were also the topic of the meeting. A rather reach session of posters was also presented.


2018 ◽  
Vol 40 (4) ◽  
pp. 333-338
Author(s):  
Ester Miranda Pereira ◽  
Adalberto Socorro da Silva ◽  
Raimundo Nonato da Silva ◽  
José Tiburcio Monte Neto ◽  
Fernando F. do Nascimento ◽  
...  

ABSTRACT Introduction: Fabry disease (FD) is a disorder caused by mutations in the gene encoding for lysosomal enzyme α-galactosidase A (α-GAL). Reduced α-GAL activity leads to progressive accumulation of globotriaosylceramide (Gb3), also known as CD77. The recent report of increased expression of CD77 in blood cells of patients with FD indicated that this molecule can be used as a potential marker for monitoring enzyme replacement therapy (ERT). Objective: The purpose of this study was to evaluate the CD77 levels throughout ERT in FD patients (V269M mutation). Methods: We evaluated the fluctuations in PBMC (peripheral blood mononuclear cell) membrane CD77 expression in FD patients undergoing ERT and correlated these levels with those observed in different cell types. Results: A greater CD77 expression was found in phagocytes of patients compared to controls at baseline. Interestingly, the variability in CD77 levels is larger in patients at baseline (340 - 1619 MIF) and after 12 months of ERT (240 - 530 MIF) compared with the control group (131 - 331 MFI). Furthermore, by analyzing the levels of CD77 in phagocytes from patients throughout ERT, we found a constant decrease in CD77 levels. Conclusion: The increased CD77 levels in the phagocytes of Fabry carriers together with the decrease in CD77 levels throughout ERT suggest that measuring CD77 levels in phagocytes is a promising tool for monitoring the response to ERT in FD.


JMED Research ◽  
2015 ◽  
pp. 1-15
Author(s):  
Jan-Ove Johansson ◽  
◽  
Jarl Ahlmén ◽  
Anita Persson ◽  
Kenneth Caidahl ◽  
...  

2020 ◽  
Vol 9 (1) ◽  
Author(s):  
E. Dolan ◽  
A. Dumas ◽  
K. M. Keane ◽  
G. Bestetti ◽  
L. H. M. Freitas ◽  
...  

Abstract Background Bone is a plastic tissue that is responsive to its physical environment. As a result, exercise interventions represent a potential means to influence the bone. However, little is currently known about how various exercise and participant characteristics interact to influence bone metabolism. Acute, controlled, interventions provide an in vivo model through which the acute bone response to exercise can be investigated, typically by monitoring circulating bone biomarkers. Currently, substantial heterogeneity in factors such as study design, quality, exercise, and participant characteristics render it difficult to synthesize and evaluate the available evidence. Using a systematic review and meta-analytic approach, the aim of this investigation is to quantify the effect of an acute exercise bout on circulating bone biomarkers as well as examine the potential factors that may moderate this response, e.g., variation in participant, exercise, and sampling characteristics. Methods This protocol was designed in accordance with the PRISMA-P guidelines. Seven databases (MEDLINE, Embase, Sport Discus, Cochrane CENTRAL, PEDro, LILACS, and Ibec) will be systematically searched and supplemented by a secondary screening of the reference lists of all included articles. The PICOS (Population, Intervention, Comparator, Outcomes and Study Design) approach was used to guide the determination of the eligibility criteria. Participants of any age, sex, training, or health status will be considered for inclusion. We will select studies that have measured the bone biomarker response before and after an acute exercise session. All biomarkers considered to represent the bone metabolism will be considered for inclusion, and sensitivity analyses will be conducted using reference biomarkers for the measurement of bone resorption and formation (namely β-CTX-1 and P1NP). Multi-level, meta-regression models within a Bayesian framework will be used to explore the main effect of acute exercise on bone biomarkers as well as potential moderating factors. The risk of bias for each individual study will be evaluated using a modified version of the Downs and Black checklist while certainty in resultant outcomes will be assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Discussion A better understanding of the bone metabolic response to an acute bout of exercise has the potential to advance our understanding of the mechanisms through which this stimulus impacts bone metabolism, including factors that may moderate this response. Additionally, we will identify current gaps in the evidence base and provide recommendations to inform future research. Systematic review registration This protocol was prospectively registered in the Open Science Framework Registry (https://osf.io/6f8dz)


2014 ◽  
Vol 21 (Suppl 1) ◽  
pp. A38.1-A38
Author(s):  
LR López Giménez ◽  
A Gómez Esteban ◽  
C Abraira Meriel ◽  
E Martinez de Ilarduya Bolado ◽  
A Colón López de Dicastillo ◽  
...  

2004 ◽  
Vol 53 (4) ◽  
pp. 331-337 ◽  
Author(s):  
Hideki TSUTSUMI ◽  
Koichi KATAGIRI ◽  
Satoshi TAKEDA ◽  
Tetsuo NASU ◽  
Sinichi IGARASHI ◽  
...  
Keyword(s):  

Sign in / Sign up

Export Citation Format

Share Document