BMP3 Affects Cortical and Trabecular Long Bone Development in Mice

Banovac, Ivan; Grgurević, Lovorka; Rumenovic, Viktorija; Vukičević, Slobodan; Erjavec, Igor

doi:10.3390/ijms23020785

Cited by 8 publications

(4 citation statements)

References 56 publications

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“…Furthermore, BMP3 serves as a target of miR-450b to regulate bone formation [ 37 ]. A recent study has presented that bone mineralization was enhanced in BMP3−/− mice, suggesting that BMP3 could influence long bone development in mice [ 38 ]. In this study, experiments of the luciferase assay showed that the suppression of miR-181a-5p increased luciferase activity while the overexpression decreased it.…”

Section: Discussionmentioning

confidence: 99%

“…The scanning resolution was set at 18 μm and 3D reconstruction of trabecular bone was used by Ctvol software. Parameters computed from these data include trabecular thickness (Tb.Th), trabecular number (Tb.N), trabecular separation (Tb.Sp), trabecular pattern factor (Tb.Pf), bone volume fraction (BV/TV) and bone surface density (BS/TV) [ 38 , 42 ].…”

Section: Methodsmentioning

confidence: 99%

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MiR-181a-5p promotes osteogenesis by targeting BMP3

Long

Dou

Cai

et al. 2023

Aging

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High-throughput microRNA (miRNA) sequencing of osteoporosis was analyzed from the Gene Expression Omnibus (GEO) database to investigate specific microRNAs that control osteogenesis. MiR-181a-5p was differentially expressed among healthy subjects and those with osteoporosis. Inhibitors and mimics were transfected into cells to modulate miR-181a-5p levels to examine the role in MC3T3-E1 functions. Alkaline phosphatase (ALP) staining and Alizarin Red S (ARS) staining were used for morphological detection, and proteins of ALP and Runt-related transcription factor 2 (RUNX2), as osteogenesis markers, were detected. During the osteogenic differentiation of MC3T3-E1, the transcription level of miR-181a-5p was significantly increased. The inhibition of miR-181a-5p suppressed MC3T3-E1 osteogenic differentiation, whereas its overexpression functioned oppositely. Consistently, the miR-181a-5p antagomir aggravated osteoporosis in old mice. Additionally, we predicted potential target genes via TargetScan and miRDB and identified bone morphogenetic protein 3 (BMP3) as the target gene. Moreover, the reduced expression of miR-181a-5p was validated in our hospitalized osteoporotic patients. These findings have substantial implications for the strategies targeting miR-181a-5p to prevent osteoporosis and potential related fractures.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

MiR-181a-5p promotes osteogenesis by targeting BMP3

Long

Dou

Cai

et al. 2023

Aging

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“…In vitro experiments using pluripotent mesenchymal progenitor C3H10T1/2 cells and preosteoblastic C2C12 cells showed that BMP-2, -6, and -9 exhibit high ability to induce both early and late osteogenic markers as well as matrix mineralization, while most BMPs can effectively promote the terminal differentiation of committed osteoblastic precursors and osteoblasts ( 18 , 19 ). In contrast to other BMPs, BMP3 has been proposed to act as an inhibitor of osteogenic BMPs and antagonizes the osteogenic activity of BMP-2, -4, -6, -7, and -9 ( 20 ), while deletion of Bmp 3 gene results in increased skeletal bone volume ( 21 ).…”

Section: General Aspects Of Bmp Familymentioning

confidence: 99%

The Role Of BMPs in the Regulation of Osteoclasts Resorption and Bone Remodeling: From Experimental Models to Clinical Applications

2022

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In response to mechanical forces and the aging process, bone in the adult skeleton is continuously remodeled by a process in which old and damaged bone is removed by bone-resorbing osteoclasts and subsequently is replaced by new bone by bone-forming cells, osteoblasts. During this essential process of bone remodeling, osteoclastic resorption is tightly coupled to osteoblastic bone formation. Bone-resorbing cells, multinuclear giant osteoclasts, derive from the monocyte/macrophage hematopoietic lineage and their differentiation is driven by distinct signaling molecules and transcription factors. Critical factors for this process are Macrophage Colony Stimulating Factor (M-CSF) and Receptor Activator Nuclear Factor-κB Ligand (RANKL). Besides their resorption activity, osteoclasts secrete coupling factors which promote recruitment of osteoblast precursors to the bone surface, regulating thus the whole process of bone remodeling. Bone morphogenetic proteins (BMPs), a family of multi-functional growth factors involved in numerous molecular and signaling pathways, have significant role in osteoblast-osteoclast communication and significantly impact bone remodeling. It is well known that BMPs help to maintain healthy bone by stimulating osteoblast mineralization, differentiation and survival. Recently, increasing evidence indicates that BMPs not only help in the anabolic part of bone remodeling process but also significantly influence bone catabolism. The deletion of the BMP receptor type 1A (BMPRIA) in osteoclasts increased osteoblastic bone formation, suggesting that BMPR1A signaling in osteoclasts regulates coupling to osteoblasts by reducing bone-formation activity during bone remodeling. The dual effect of BMPs on bone mineralization and resorption highlights the essential role of BMP signaling in bone homeostasis and they also appear to be involved in pathological processes in inflammatory disorders affecting bones and joints. Certain BMPs (BMP2 and -7) were approved for clinical use; however, increased bone resorption rather than formation were observed in clinical applications, suggesting the role BMPs have in osteoclast activation and subsequent osteolysis. Here, we summarize the current knowledge of BMP signaling in osteoclasts, its role in osteoclast resorption, bone remodeling, and osteoblast–osteoclast coupling. Furthermore, discussion of clinical application of recombinant BMP therapy is based on recent preclinical and clinical studies.

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“…BMP2 is a primary participant in postnatal skeletal homeostasis through its regulation of SSC niches and BMP2 signaling is required for the di erentiation of osteoprogenitor cells into the fully functioning osteoblasts (50). On the other hand, the role of BMP3 has never been fully elucidated (51)(52)(53) but recent discoveries presented at the Conference highlighted a novel role of BMP3 in enabling chondrocyte di erentiation following decreased expression of BMP3 and ALK2.…”

Section: Bone: Diseases and Regenerationmentioning

confidence: 99%

State-of-the-art of the Bone Morphogenetic Protein research field: 13th International BMP Conference, Dubrovnik 2022

Štoković¹,

Ivanjko²,

Jelić³

et al. 2022

Rad Hrvatske akademije znanosti i umjetnosti

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who got an insight into the latest achievements in basic, translational, and clinical research of BMP molecules through 75 lectures categorized into several scienti c sections. is review paper provides the most important novel ndings on the structure, function, and signaling of BMPs, the role of BMPs in patterning and organoids as well as the role of BMP in metabolism. Moreover, we discussed the role of BMPs in various diseases including cancer pathogenesis, pulmonary arterial hypertension, and brodysplasia ossi cans progressiva (FOP). Finally, we provided an overview of the new BMP-based therapies in regenerative medicine that are currently in di erent stages of preclinical and clinical trials.

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BMP3 Affects Cortical and Trabecular Long Bone Development in Mice

Cited by 8 publications

References 56 publications

MiR-181a-5p promotes osteogenesis by targeting BMP3

MiR-181a-5p promotes osteogenesis by targeting BMP3

The Role Of BMPs in the Regulation of Osteoclasts Resorption and Bone Remodeling: From Experimental Models to Clinical Applications

State-of-the-art of the Bone Morphogenetic Protein research field: 13th International BMP Conference, Dubrovnik 2022

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