The Role of BMP Signaling in Osteoclast Regulation

Heubel, Brian; Nohe, Anja

doi:10.3390/jdb9030024

Cited by 25 publications

(19 citation statements)

References 193 publications

(270 reference statements)

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“…Irregular activities of these bone cells can lead to juvenile osteoporosis in childhood, or osteopenia and osteoporosis later in adulthood [ 5 , 54 ]. While it is suggested that these bone disorders may arise due to hyperactivity of osteoclasts, the function of these bone resorption cells isolated directly from humans is not established [ 1 , 18 ]. Therefore, there is an urgent need to establish a reliable method of isolating viable bone marrow cells that can be differentiated into osteoclasts.…”

Section: Discussionmentioning

confidence: 99%

“…Osteoblasts are mononucleated cells responsible for forming new bone and derive from mesenchymal stem cell (MSC) progenitors [ 11 , 12 , 13 , 14 ]. Contrarily, osteoclasts are multinucleated immune cells that derive from hematopoietic stem cells (HSCs) and resorb old or damaged bone [ 8 , 10 , 15 , 16 , 17 , 18 ]. The crosstalk between these two cell types is critical for the formation of early structures, such as digits, and bone homeostasis throughout adulthood [ 1 , 19 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

“…The monocytes/macrophages can then terminally differentiate into functional osteoclasts, which will be responsible for resorbing bone ( Figure 1 ). The M-CSF and RANKL signaling pathways promote cell differentiation, survival, and proliferation by activating the Akt, Erk, NF-κB, and MAPK pathways [ 18 ]. It has previously been reported that murine RAW264.7 cells of the monocyte/macrophage lineage respond to these factors and can be used as a model for studying osteoclastogenesis [ 16 , 27 ].…”

Section: Introductionmentioning

confidence: 99%

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Differentiation of Cells Isolated from Human Femoral Heads into Functional Osteoclasts

Halloran

Heubel

MacMurray

et al. 2022

JDB

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Proper formation of the skeleton during development is crucial for the mobility of humans and the maintenance of essential organs. The production of bone is regulated by osteoblasts and osteoclasts. An imbalance of these cells can lead to a decrease in bone mineral density, which leads to fractures. While many studies are emerging to understand the role of osteoblasts, less studies are present about the role of osteoclasts. This present study utilized bone marrow cells isolated directly from the bone marrow of femoral heads obtained from osteoarthritic (OA) patients after undergoing hip replacement surgery. Here, we used tartrate resistant acid phosphatase (TRAP) staining, Cathepsin K, and nuclei to identity osteoclasts and their functionality after stimulation with macrophage-colony stimulation factor (M-CSF) and receptor activator of nuclear factor kappa-β ligand (RANKL). Our data demonstrated that isolated cells can be differentiated into functional osteoclasts, as indicated by the 92% and 83% of cells that stained positive for TRAP and Cathepsin K, respectively. Furthermore, isolated cells remain viable and terminally differentiate into osteoclasts when stimulated with RANKL. These data demonstrate that cells isolated from human femoral heads can be differentiated into osteoclasts to study bone disorders during development and adulthood.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Differentiation of Cells Isolated from Human Femoral Heads into Functional Osteoclasts

Halloran

Heubel

MacMurray

et al. 2022

JDB

Self Cite

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“…BMPs are a group of proteins that belong to the superfamily of transforming growth factor-β (TGF-β) [ 41 ]. These proteins were initially discovered for their osteoinductive properties [ 42 ]. Nowadays, BMPs are extensively studied in animal models of bone regeneration.…”

Section: Discussionmentioning

confidence: 99%

Nano-Hydroxyapatite as a Delivery System for Promoting Bone Regeneration In Vivo: A Systematic Review

Zaffarin

et al. 2021

Nanomaterials

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Nano-hydroxyapatite (nHA) has been widely used as an orthopedic biomaterial and vehicle for drug delivery owing to its chemical and structural similarity to bone minerals. Several studies have demonstrated that nHA based biomaterials have a potential effect for bone regeneration with very minimal to no toxicity or inflammatory response. This systematic review aims to provide an appraisal of the effectiveness of nHA as a delivery system for bone regeneration and whether the conjugation of proteins, antibiotics, or other bioactive molecules to the nHA further enhances osteogenesis in vivo. Out of 282 articles obtained from the literature search, only 14 articles met the inclusion criteria for this review. These studies showed that nHA was able to induce bone regeneration in various animal models with large or critical-sized bone defects, open fracture, or methicillin-resistant Staphylococcus aureus (MRSA)-induced osteomyelitis. The conjugations of drugs or bioactive molecules such as bone-morphogenetic protein-2 (BMP-2), vancomycin, calcitriol, dexamethasone, and cisplatin were able to enhance the osteogenic property of nHA. Thus, nHA is a promising delivery system for a variety of compounds in promoting bone regeneration in vivo.

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“…It is known that BMP2 and -7 increase osteoblastic differentiation markers ( 34 , 90 ), and that BMP signaling promotes chondrocyte differentiation ( 91 ). By acting on osteoblasts and chondrocytes, BMPs enable process of endochondral bone formation and ossification ( 92 ). In osteoblasts, BMPs act in a complex interaction with several signaling pathways, including Wnt, Notch, Hedgehog and FGF ( 89 , 93 ).…”

Section: Bmp Function In Osteoclastsmentioning

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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The Role of BMP Signaling in Osteoclast Regulation

Cited by 25 publications

References 193 publications

Differentiation of Cells Isolated from Human Femoral Heads into Functional Osteoclasts

Differentiation of Cells Isolated from Human Femoral Heads into Functional Osteoclasts

Nano-Hydroxyapatite as a Delivery System for Promoting Bone Regeneration In Vivo: A Systematic Review

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

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