Regulation of osteoblasts by alkaline phosphatase in ankylosing spondylitis

Jo, Sungsin; Han, Jinil; Lee, Young L.; Yoon, Subin; Lee, Jae-Hyun; Wang, Sung Eun; Kim, So Yeon

doi:10.1111/1756-185x.13419

Cited by 37 publications

(28 citation statements)

References 22 publications

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“…As the induction time increased, the expression of most genes increased gradually, while COL1A2 expression peaked its maximum on the 21st day, consistent with findings of Yoo et al regarding COL expression [48]. The expression of ALPL is used to evaluate the activity of osteoblasts, and high ALPL expression is considered a key indicators of osteoblast induction [49]. The expression of ALPL increasing the induction time in the current study.…”

Section: Discussionsupporting

confidence: 90%

Pathways involved in pony body size development

et al. 2021

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Background The mechanism of body growth in mammals is poorly understood. Here, we investigated the regulatory networks involved in body growth through transcriptomic analysis of pituitary and epiphyseal tissues of smaller sized Debao ponies and Mongolian horses at the juvenile and adult stages. Results We found that growth hormone receptor (GHR) was expressed at low levels in long bones, although growth hormone (GH) was highly expressed in Debao ponies compared with Mongolian horses. Moreover, significant downregulated of the GHR pathway components m-RAS and ATF3 was found in juvenile ponies, which slowed the proliferation of bone osteocytes. However, WNT2 and PLCβ2 were obviously upregulated in juvenile Debao ponies, which led to premature mineralization of the bone extracellular matrix. Furthermore, we found that the WNT/Ca2+ pathway may be responsible for regulating body growth. GHR was demonstrated by q-PCR and Western blot analyses to be expressed at low levels in long bones of Debao ponies. Treatment with WNT antagonistI decreased the expression of WNT pathway components (P < 0.05) in vitro. Transduction of ATDC5 cells with a GHR-RNAi lentiviral vector decreased the expression of the GHR pathway components (P < 0.05). Additionally, the expression of the IGF-1 gene in the liver was lower in Debao ponies than in Mongolian horses at the juvenile and adult stages. Detection of plasma hormone concentrations showed that Debao ponies expressed higher levels of IGF-1 as juveniles and higher levels of GH as adults than Mongolian horses, indicating that the hormone regulation in Debao ponies differs from that in Mongolian horses. Conclusion Our work provides insights into the genetic regulation of short stature growth in mammals and can provide useful information for the development of therapeutic strategies for small size.

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Section: Discussionsupporting

confidence: 90%

Pathways involved in pony body size development

et al. 2021

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“…As an early marker of osteogenic differentiation, ALP content increases, and its activity elevation can improve the phosphate content in cells, thereby promoting extracellular matrix calcification and bone growth. 23 To further verify the functional effect of miR-149-3p on osteogenic differentiation, we transfected hADSCs with miR-149-3p mimic, conducted osteogenic induction and observed a significant increase in mineral calcium deposits and ALP activity in hADSCs, which is consistent with the findings of a previous study. 7 As a key transcription factor in osteogenic differentiation, RUNX2 decides and initiates osteogenic differentiation of hADSCs.…”

Section: Discussionsupporting

confidence: 87%

MiR‐149‐3p can improve the osteogenic differentiation of human adipose‐derived stem cells via targeting AKT1

Lai

Zhou

Chen

et al. 2021

The Kaohsiung J of Med Scie

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The study aims to investigate the role of microRNA-149-3p (miR-149-3p) in regulating osteogenic differentiation of human adipose-derived stem cells (hADSCs) by targeting v-akt murine thymoma viral oncogene homolog 1 (AKT1). Bioinformatics websites and a dual luciferase reporter assay were used to predict and verify the targeting relationship between miR-149-3p and AKT1. The hADSCs were divided into the blank, negative control (NC), mimic, control siRNA, AKT1 siRNA, and miR-149-3p inhibitors + AKT1 siRNA groups and then subjected to Alizarin Red staining, Alkaline phosphatase (ALP) staining, ALP activity detections, MTT assay, and EdU cell proliferation assay. Gene or protein expression was quantified using quantitative real-time PCR (qRT-PCR) or Western blotting, respectively. The miR-149-3p expression increased gradually and AKT1 expression decreased gradually during osteogenic differentiation of hADSCs. The prediction of bioinformatics websites miRTarBase and TargetScan and the dual luciferase reporter assay indicated that miR-149-3p can directly target AKT1. After hADSCs were transfected with miR-149-3p mimic, AKT1 expression was significantly downregulated. However, transfection with AKT1 siRNA did not have an impact on miR-149-3p in hADSCs. In comparison with the AKT1 siRNA group, the miR-149-3p inhibitors + AKT1 siRNA group showed decreased miR-149-3p expression but increased AKT1 expression. In addition, AKT1 siRNA enhanced the cell viability and proliferation of hADSCs and increased mineral calcium deposition and ALP activity, resulting in higher expression of osteogenic differentiation-related genes, which was reversed by miR-149-3p inhibition. The miR-149-3p can increase the expression of osteogenic differentiation-related genes by targeting AKT1 and thereby enhance the osteogenic differentiation of hADSCs.

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“…The activity of alkaline phosphatase (ALP) is one of the most important indexes to judge the differentiation and maturation of osteoblasts. 20 We used a microplate reader to examine the ALP activity in the present study, finding that ALP activity was significantly decreased in the miR-122 mimic group compared with the NC mimic group. In addition, ALP activity was enhanced in the miR-122 inhibitor group compared with the NC inhibitor group (p < 0.05; Figure 7A).…”

Section: Overexpression Of Mir-122 Inhibits Pcp4 Expressionmentioning

confidence: 85%

miR-122 Exerts Inhibitory Effects on Osteoblast Proliferation/Differentiation in Osteoporosis by Activating the PCP4-Mediated JNK Pathway

Meng

Lin

Jiang

et al. 2020

Molecular Therapy - Nucleic Acids

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Osteoporosis is characterized by the reduction of bone mineral density and deterioration of bone quality which leads to high risk of fractures. Some microRNAs (miRNAs) have been confirmed as potential modulators of osteoblast differentiation to maintain bone mass maintenance. We aimed to clarify whether miR-122 could regulate osteoblast differentiation in ovariectomized rats with osteoporosis. miR-122 was upregulated and Purkinje cell protein 4 (PCP4) was downregulated in ovariectomized rats. PCP4 was identified as a target of miR-122 by dual-luciferase reporter gene assay. We transfected isolated osteoblasts from ovariectomized rats with miR-122 mimic or inhibitor or PCP4 overexpression vectors. Proliferation and differentiation of osteoblasts were repressed by the overexpression of miR-122 but enhanced by overexpression of PCP4. miR-122 could induce the activation of the c-Jun NH2-terminal kinase (JNK) signaling pathway, while PCP4 blocked this pathway. Rescue experiments further demonstrated that the inhibiting effects of miR-122 on osteoblast differentiation could be compensated by activation of the PCP4 or inhibition of JNK signaling pathway. Collectively, our data imply that miR-122 inhibits osteoblast proliferation and differentiation in rats with osteoporosis, highlighting a novel therapeutic target for osteoporotic patients.

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Regulation of osteoblasts by alkaline phosphatase in ankylosing spondylitis

Cited by 37 publications

References 22 publications

Pathways involved in pony body size development

Pathways involved in pony body size development

MiR‐149‐3p can improve the osteogenic differentiation of human adipose‐derived stem cells via targeting AKT1

miR-122 Exerts Inhibitory Effects on Osteoblast Proliferation/Differentiation in Osteoporosis by Activating the PCP4-Mediated JNK Pathway

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