The Bone Morphogenetic Protein Pathway: The Osteoclastic Perspective

Lademann, Franziska; Hofbauer, Lorenz C.; Rauner, Martina

doi:10.3389/fcell.2020.586031

Cited by 29 publications

(23 citation statements)

References 73 publications

(108 reference statements)

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“…Bone morphogenetic proteins (BMPs) are also emerging as key players in osteoclast homeostasis and appear to interact with the RANKL pathway in OCL differentiation and activation. The role of BMPs in OCL signaling is reviewed on a separate contribution to this Research Topic (Lademann et al, 2020) and will not be further discussed here.…”

Section: The M-csf Pathway Controls the Survival And Proliferation Of Ocl Precursorsmentioning

confidence: 99%

Role of OSCAR Signaling in Osteoclastogenesis and Bone Disease

Nedeva

Vitale

Elson

et al. 2021

Front. Cell Dev. Biol.

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Formation of mature bone-resorbing cells through osteoclastogenesis is required for the continuous remodeling and repair of bone tissue. In aging and disease this process may become aberrant, resulting in excessive bone degradation and fragility fractures. Interaction of receptor-activator of nuclear factor-κB (RANK) with its ligand RANKL activates the main signaling pathway for osteoclastogenesis. However, compelling evidence indicates that this pathway may not be sufficient for the production of mature osteoclast cells and that co-stimulatory signals may be required for both the expression of osteoclast-specific genes and the activation of osteoclasts. Osteoclast-associated receptor (OSCAR), a regulator of osteoclast differentiation, provides one such co-stimulatory pathway. This review summarizes our present knowledge of osteoclastogenesis signaling and the role of OSCAR in the normal production of bone-resorbing cells and in bone disease. Understanding the signaling mechanism through this receptor and how it contributes to the production of mature osteoclasts may offer a more specific and targeted approach for pharmacological intervention against pathological bone resorption.

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Section: The M-csf Pathway Controls the Survival And Proliferation Of Ocl Precursorsmentioning

confidence: 99%

Role of OSCAR Signaling in Osteoclastogenesis and Bone Disease

Nedeva

Vitale

Elson

et al. 2021

Front. Cell Dev. Biol.

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“…Among wide variety of potential coupling factors [presented in ( 60 )], BMPs have significant role in this process, and central role might have BMP receptor type IA ( 65 ), as seen from studies on animal knockout models. Mice with deletion of BMPRIA in osteoclasts showed increased osteoblastic bone formation, which suggests that BMPRIA signaling in osteoclasts negatively regulates osteoblast differentiation and bone mass ( 66 , 67 ).…”

Section: Role Of Osteoclasts In Bone Remodelingmentioning

confidence: 99%

“…Recently, SMAD1/5 suggested to be regulatory pathway for osteoblast-osteoclast coupling via WNT and sphingosine kinase (SPHK1) ( 68 ). Collectively, BMPs act as important mediators in osteoblast-osteoclast communication and thus balance the rate of bone remodeling process ( 69 ), which could be of significant importance when considering potential therapies targeting BMP signaling pathways ( 65 ).…”

Section: Role Of Osteoclasts In Bone Remodelingmentioning

confidence: 99%

“…Among multiple types of BMPs tested, BMP6 was one of most potent osteogenic BMPs ( 18 , 109 , 126 ), also due to its resistance to noggin ( 127 ), but it seems to be less potent in stimulation of osteoclasts than in osteoblasts ( 65 , 108 , 128 ). Structurally closely related to BMP5, BMP6 has also been shown to have stimulatory effect on osteoclasts at some concentrations, although both, BMP5 and BMP6, were less effective in stimulating osteoclastogenesis in comparison with BMP2 ( 108 ).…”

Section: Bmp Function In Osteoclastsmentioning

confidence: 99%

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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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“…Several growth factors have been explored for their capacity to advance the healing process of bone tissue, but bone morphogenetic proteins (BMPs) are among the most proficient. Those multifunctional cytokines play a pivotal role in bone remodeling, both during osteoblastogenesis and osteoclast homeostasis [54,55]. BMPs are extensively explored for orthopedics and oral maxillofacial surgery [56][57][58].…”

Section: Introductionmentioning

confidence: 99%

Bioactive Coatings Loaded with Osteogenic Protein for Metallic Implants

Gherasim

Grumezescu

et al. 2021

Polymers

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Osteoconductive and osteoinductive coatings represent attractive and tunable strategies towards the enhanced biomechanics and osseointegration of metallic implants, providing accurate local modulation of bone-to-implant interface. Composite materials based on polylactide (PLA) and hydroxyapatite (HAp) are proved beneficial substrates for the modulation of bone cells’ development, being suitable mechanical supports for the repair and regeneration of bone tissue. Moreover, the addition of osteogenic proteins represents the next step towards the fabrication of advanced biomaterials for hard tissue engineering applications, as their regulatory mechanisms beneficially contribute to the new bone formation. In this respect, laser-processed composites, based on PLA, Hap, and bone morphogenetic protein 4(BMP4), are herein proposed as bioactive coatings for metallic implants. The nanostructured coatings proved superior ability to promote the adhesion, viability, and proliferation of osteoprogenitor cells, without affecting their normal development and further sustaining the osteogenic differentiation of the cells. Our results are complementary to previous studies regarding the successful use of chemically BMP-modified biomaterials in orthopedic and orthodontic applications.

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The Bone Morphogenetic Protein Pathway: The Osteoclastic Perspective

Cited by 29 publications

References 73 publications

Role of OSCAR Signaling in Osteoclastogenesis and Bone Disease

Role of OSCAR Signaling in Osteoclastogenesis and Bone Disease

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

Bioactive Coatings Loaded with Osteogenic Protein for Metallic Implants

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