BMP9 Prevents Bone Loss in Ovariectomized Mice by Dual Regulation of Bone Remodeling

Author(s):  
Yan-man Zhou ◽  
Yu-ying Yang ◽  
Yi-xuan Jing ◽  
Tian-jiao Yuan ◽  
Li-hao Sun ◽  
...  
2020 ◽  
Vol 35 (5) ◽  
pp. 978-993 ◽  
Author(s):  
Yan‐Man Zhou ◽  
Yu‐Ying Yang ◽  
Yi‐Xuan Jing ◽  
Tian‐Jiao Yuan ◽  
Li‐Hao Sun ◽  
...  

Author(s):  
Wei Yu ◽  
Leilei Zhong ◽  
Lutian Yao ◽  
Yulong Wei ◽  
Tao Gui ◽  
...  

AbstractBone is maintained by coupled activities of bone-forming osteoblasts/osteocytes and bone-resorbing osteoclasts and an alternation of this relationship can lead to pathologic bone loss such as in osteoporosis. It is well known that osteogenic cells support osteoclastogenesis via synthesizing RANKL. Interestingly, our recently identified bone marrow mesenchymal cell population—marrow adipogenic lineage precursors (MALPs) that form a multi-dimensional cell network in bone—was computationally demonstrated to be the most interactive with monocyte-macrophage lineage cells through highly and specifically expressing several osteoclast regulatory factors, including RANKL. Using an adipocyte-specific Adipoq-Cre to label MALPs, we demonstrated that mice with RANKL deficiency in MALPs have a drastic increase of trabecular bone mass in long bones and vertebrae starting from 1 month of age but that their cortical bone is normal. This phenotype was accompanied by diminished osteoclast number and attenuated bone formation at the trabecular bone surface. Reduced RANKL signaling in calvarial MALPs also abolished osteolytic lesions after lipopolysaccharide (LPS) injections. Furthermore, in ovariectomized mice, elevated bone resorption was partially attenuated by RANKL deficiency in MALPs. In summary, our studies identified MALPs as a critical player in controlling bone remodeling during normal bone metabolism and pathological bone loss in a RANKL-dependent fashion.


2017 ◽  
Vol 195 ◽  
pp. 137-142 ◽  
Author(s):  
Mi Hye Kim ◽  
Hye Ji Lee ◽  
Jung-Chul Park ◽  
Jongki Hong ◽  
Woong Mo Yang

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Mengge Sun ◽  
Xiaoya Zhou ◽  
Lili Chen ◽  
Shishu Huang ◽  
Victor Leung ◽  
...  

MicroRNAs are involved in many cellular and molecular activities and played important roles in many biological and pathological processes, such as tissue formation, cancer development, diabetes, neurodegenerative diseases, and cardiovascular diseases. Recently, it has been reported that microRNAs can modulate the differentiation and activities of osteoblasts and osteoclasts, the key cells that are involved in bone remodeling process. Meanwhile, the results from our and other research groups showed that the expression profiles of microRNAs in the serum and bone tissues are significantly different in postmenopausal women with or without fractures compared to the control. Therefore, it can be postulated that microRNAs might play important roles in bone remodeling and that they are very likely to be involved in the pathological process of postmenopausal osteoporosis. In this review, we will present the updated research on the regulatory roles of microRNAs in osteoblasts and osteoclasts and the expression profiles of microRNAs in osteoporosis and osteoporotic fracture patients. The perspective of serum microRNAs as novel biomarkers in bone loss disorders such as osteoporosis has also been discussed.


Oncotarget ◽  
2017 ◽  
Vol 8 (44) ◽  
pp. 76558-76573 ◽  
Author(s):  
Ting Zheng ◽  
Ju-Hee Kang ◽  
Jung-Sun Sim ◽  
Jung-Woo Kim ◽  
Jeong-Tae Koh ◽  
...  

Bone ◽  
2020 ◽  
Vol 135 ◽  
pp. 115316 ◽  
Author(s):  
Nana Takakura ◽  
Miho Matsuda ◽  
Masud Khan ◽  
Fumitaka Hiura ◽  
Kazuhiro Aoki ◽  
...  

Nutrients ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1831 ◽  
Author(s):  
Youn-Hwan Hwang ◽  
Seon-A Jang ◽  
Taesoo Kim ◽  
Hyunil Ha

In traditional oriental medicine, the fruit of Forsythia suspensa has been used as a nutritional supplement to alleviate inflammation and treat gastrointestinal diseases. However, there is no information available on its beneficial effects on bone. We investigated the beneficial effects of F. suspensa water extract (WFS) on osteoclast differentiation and bone loss. The microarchitecture of trabecular bone was analyzed by micro-computed tomography. Osteoclast differentiation was evaluated based on tartrate-resistant alkaline phosphatase activity, and bone resorption activity was examined on a bone-like mineral surface. The mechanism of action of WFS was assessed by evaluating the expression and activation of signaling molecules. Phytochemical constituents were identified and quantitated by ultrahigh-performance liquid chromatography–tandem mass spectrometry. WFS reduced ovariectomy-induced trabecular bone loss and inhibited receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation and resorption activity. WFS suppressed RANKL-induced expression of nuclear factor of activated T cells cytoplasmic 1, a crucial transcription factor for osteoclast differentiation by decreasing c-Fos protein levels and suppressing the activation of p38 and c-Jun-N-terminal kinase. We also identified 12 phytochemicals in WFS including lignans, phenylethanoids, and flavonoids. Collectively, these results suggest that WFS inhibits osteoclast differentiation and can potentially be used to treat postmenopausal osteoporosis.


2018 ◽  
Vol 4 (4) ◽  
pp. 37 ◽  
Author(s):  
Giuseppina E. Grieco ◽  
Dorica Cataldo ◽  
Elena Ceccarelli ◽  
Laura Nigi ◽  
Giovanna Catalano ◽  
...  

Type 1 diabetes (T1D) is characterized by bone loss and altered bone remodeling, resulting into reduction of bone mineral density (BMD) and increased risk of fractures. Identification of specific biomarkers and/or causative factors of diabetic bone fragility is of fundamental importance for an early detection of such alterations and to envisage appropriate therapeutic interventions. MicroRNAs (miRNAs) are small non-coding RNAs which negatively regulate genes expression. Of note, miRNAs can be secreted in biological fluids through their association with different cellular components and, in such context, they may represent both candidate biomarkers and/or mediators of bone metabolism alterations. Here, we aimed at identifying miRNAs differentially expressed in serum of T1D patients and potentially involved in bone loss in type 1 diabetes. We selected six miRNAs previously associated with T1D and bone metabolism: miR-21; miR-24; miR-27a; miR-148a; miR-214; and miR-375. Selected miRNAs were analyzed in sera of 15 T1D patients (age: 33.57 ± 8.17; BMI: 21.4 ± 1.65) and 14 non-diabetic subjects (age: 31.7 ± 8.2; BMI: 24.6 ± 4.34). Calcium, osteocalcin, parathormone (PTH), bone ALkaline Phoshatase (bALP), and Vitamin D (VitD) as well as main parameters of bone health were measured in each patient. We observed an increased expression of miR-148a (p = 0.012) and miR-21-5p (p = 0.034) in sera of T1D patients vs non-diabetic subjects. The correlation analysis between miRNAs expression and the main parameters of bone metabolism, showed a correlation between miR-148a and Bone Mineral Density (BMD) total body (TB) values (p = 0.042) and PTH circulating levels (p = 0.033) and the association of miR-21-5p to Bone Mineral Content-Femur (BMC-FEM). Finally, miR-148a and miR-21-5p target genes prediction analysis revealed several factors involved in bone development and remodeling, such as MAFB, WNT1, TGFB2, STAT3, or PDCD4, and the co-modulation of common pathways involved in bone homeostasis thus potentially assigning a role to both miR-148a and miR-21-5p in bone metabolism alterations. In conclusion, these results lead us to hypothesize a potential role for miR-148a and miR-21-5p in bone remodeling, thus representing potential biomarkers of bone fragility in T1D.


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