Parathyroid Hormone-regulation of Runx2 by MiR-290 for Matrix Metalloproteinase-13 Expression in Rat Osteoblastic Cells

2021 ◽  
Vol 21 ◽  
Author(s):  
N Akshaya ◽  
N Srinaath ◽  
M Rohini ◽  
R Ilangovan ◽  
N Selvamurugan
Keyword(s):  
Parathyroid Hormone ◽  
Bone Metabolism ◽  
Bone Remodeling ◽  
Mirna Profile ◽  
Osteoblastic Cells ◽  
Luciferase Reporter ◽  
Hormone Regulation ◽  
Bone Disorders ◽  
Matrix Metalloproteinase 13 ◽  
Direct Targeting

Background: The dynamic changes that bone undergoes during the ensemble of remodeling are administered by vital factors like Runx2 (a bone transcription factor) and matrix metalloproteinases (MMPs). Aims: Parathyroid hormone (PTH), an FDA approved drug for bone-related ailments, was seen to stimulate MMP-13 expression via Runx2 to ultimately aid in the bone remodeling process. MicroRNAs (miRNAs) have been shown to play a major role in controlling bone metabolism, and the use of miRNAs has recently become promising therapeutic avenues for the treatment of many diseases, including bone disorders. Thus, in this study, we attempted to investigate and evaluate the expression of MMP-13 via a miRNA profile targeting Runx2 under PTH-regulation in rat osteoblastic cells. Methods: Parathyroid hormone (PTH), an FDA approved drug for bone-related ailments, was seen to stimulate MMP-13 expression via Runx2 to ultimately aid in the bone remodeling process. MicroRNAs (miRNAs) have been shown to play a major role in controlling bone metabolism, and the use of miRNAs has recently become promising therapeutic avenues for the treatment of many diseases, including bone disorders. Thus, in this study, we attempted to investigate and evaluate the expression of MMP-13 via a miRNA profile targeting Runx2 under PTH-regulation in rat osteoblastic cells. Results: Overexpression of miR-290 decreased the expression of Runx2, the binding of Runx2 at the MMP-13 promoter, and the expression of MMP-13 mRNA in PTH-treated UMR106-01 cells. A dual luciferase reporter assay identified the direct targeting of Runx2 mRNA by miR-290 in these cells. Conclusion: Our findings indicate that the PTH-responsive miR-290 regulated Runx2-mediated MMP-13 expression in rat osteoblastic cells, suggesting miR-290 as a molecular marker or target in bone and bone-related diseases.

scholarly journals Parathyroid hormone regulation of hypoxia-inducible factor signaling in osteoblastic cells

Bone ◽  
2015 ◽  
Vol 81 ◽  
pp. 97-103 ◽  
Author(s):  
Alice Wong ◽  
Gabriela G. Loots ◽  
Clare E. Yellowley ◽  
Andréa C. Dosé ◽  
Damian C. Genetos
Keyword(s):  
Parathyroid Hormone ◽  
Hypoxia Inducible Factor ◽  
Osteoblastic Cells ◽  
Hormone Regulation

scholarly journals Osteoclast Responses to Lipopolysaccharide, Parathyroid Hormone and Bisphosphonates in Neonatal Murine Calvaria Analyzed by Laser Scanning Confocal Microscopy

2005 ◽  
Vol 53 (12) ◽  
pp. 1525-1537 ◽  
Author(s):  
Keiko Suzuki ◽  
Sadaaki Takeyama ◽  
Takashi Kikuchi ◽  
Shoji Yamada ◽  
Jaro Sodek ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Confocal Microscopy ◽  
Bone Remodeling ◽  
Laser Scanning ◽  
In Vivo Studies ◽  
Osteoblastic Cells ◽  
Type I ◽  
Αvβ3 Integrin ◽  
Sealing Zone

Because the development and activity of osteoclasts in bone remodeling is critically dependent on cell-cell and cell-matrix interactions, we used laser confocal microscopy to study the response of osteoclasts to lipopolysaccharide (LPS; 10 μg/ml), parathyroid hormone (PTH; 10−8 M), and bisphosphonates (BPs; 1–25 μM clodronate or 0.1–2.5 μM risedronate) in cultured neonatal calvaria. Following treatment with LPS or PTH (<48 hr), osteopontin (OPN) and the αvβ3 integrin were found colocalized with the actin ring in the sealing zone of actively resorbing osteoclasts. In contrast, non-resorbing osteoclasts in BP-treated cultures showed morphological abnormalities, including retraction of pseudopods and vacuolization of cytoplasm. In the combined presence of LPS and BP, bone-resorbing osteoclasts were smaller and the sealing zone diffuse, reflecting reduced actin, OPN, and β3 integrin staining. Depth analyses of calvaria showed that the area of resorbed bone was filled with proliferating osteoblastic cells that stained for alkaline phosphatase, collagen type I, and bone sialoprotein, regardless of the presence of BPs. These studies show that confocal microscopy of neonatal calvaria in culture can be used to assess the cytological relationships between osteoclasts and osteoblastic cells in response to agents that regulate bone remodeling in situ, avoiding systemic effects that can compromise in vivo studies and artifacts associated with studies of isolated osteoclasts.

Genetic Contribution to Bone Metabolism, Calcium Excretion, and Vitamin D and Parathyroid Hormone Regulation

2001 ◽  
Vol 16 (2) ◽  
pp. 371-378 ◽  
Author(s):  
D. Hunter ◽  
M. De Lange ◽  
H. Snieder ◽  
A. J. MacGregor ◽  
R. Swaminathan ◽  
...  
Keyword(s):  
Vitamin D ◽  
Parathyroid Hormone ◽  
Bone Metabolism ◽  
Calcium Excretion ◽  
Hormone Regulation ◽  
Genetic Contribution

scholarly journals HDAC4 Represses Matrix Metalloproteinase-13 Transcription in Osteoblastic Cells, and Parathyroid Hormone Controls This Repression

2010 ◽  
Vol 285 (13) ◽  
pp. 9616-9626 ◽  
Author(s):  
Emi Shimizu ◽  
Nagarajan Selvamurugan ◽  
Jennifer J. Westendorf ◽  
Eric N. Olson ◽  
Nicola C. Partridge
Keyword(s):  
Parathyroid Hormone ◽  
Matrix Metalloproteinase ◽  
Osteoblastic Cells ◽  
Matrix Metalloproteinase 13

scholarly journals The Development of Molecular Biology of Osteoporosis

2021 ◽  
Vol 22 (15) ◽  
pp. 8182
Author(s):  
Yongguang Gao ◽  
Suryaji Patil ◽  
Jingxian Jia
Keyword(s):  
Bone Resorption ◽  
Molecular Biology ◽  
Bone Formation ◽  
Bone Mass ◽  
Bone Remodeling ◽  
Bone Cells ◽  
Cell Activity ◽  
Bone Cell ◽  
Bone Disorders ◽  
Molecular Aspects

Osteoporosis is one of the major bone disorders that affects both women and men, and causes bone deterioration and bone strength. Bone remodeling maintains bone mass and mineral homeostasis through the balanced action of osteoblasts and osteoclasts, which are responsible for bone formation and bone resorption, respectively. The imbalance in bone remodeling is known to be the main cause of osteoporosis. The imbalance can be the result of the action of various molecules produced by one bone cell that acts on other bone cells and influence cell activity. The understanding of the effect of these molecules on bone can help identify new targets and therapeutics to prevent and treat bone disorders. In this article, we have focused on molecules that are produced by osteoblasts, osteocytes, and osteoclasts and their mechanism of action on these cells. We have also summarized the different pharmacological osteoporosis treatments that target different molecular aspects of these bone cells to minimize osteoporosis.

scholarly journals SLPI is a critical mediator that controls PTH-induced bone formation

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Akito Morimoto ◽  
Junichi Kikuta ◽  
Keizo Nishikawa ◽  
Takao Sudo ◽  
Maki Uenaka ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Bone Resorption ◽  
Bone Formation ◽  
Protease Inhibitor ◽  
Bone Metabolism ◽  
Serine Protease ◽  
Serine Protease Inhibitor ◽  
Secretory Leukocyte Protease Inhibitor ◽  
Bone Imaging ◽  
Genetic Ablation

AbstractOsteoclastic bone resorption and osteoblastic bone formation/replenishment are closely coupled in bone metabolism. Anabolic parathyroid hormone (PTH), which is commonly used for treating osteoporosis, shifts the balance from osteoclastic to osteoblastic, although it is unclear how these cells are coordinately regulated by PTH. Here, we identify a serine protease inhibitor, secretory leukocyte protease inhibitor (SLPI), as a critical mediator that is involved in the PTH-mediated shift to the osteoblastic phase. Slpi is highly upregulated in osteoblasts by PTH, while genetic ablation of Slpi severely impairs PTH-induced bone formation. Slpi induction in osteoblasts enhances its differentiation, and increases osteoblast–osteoclast contact, thereby suppressing osteoclastic function. Intravital bone imaging reveals that the PTH-mediated association between osteoblasts and osteoclasts is disrupted in the absence of SLPI. Collectively, these results demonstrate that SLPI regulates the communication between osteoblasts and osteoclasts to promote PTH-induced bone anabolism.

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