Bone morphogenetic proteins and cancer

Bone morphogenetic proteins (BMPs) belong to the TGF-β super family, and are essential for the regulation of foetal development, tissue differentiation and homeostasis and a multitude of cellular functions. Naturally, this has led to the exploration of aberrance in this highly regulated system as a key factor in tumourigenesis. Originally identified for their role in osteogenesis and bone turnover, attention has been turned to the potential role of BMPs in tumour metastases to, and progression within, the bone niche. This is particularly pertinent to breast cancer, which commonly metastasises to bone, and in which studies have revealed aberrations of both BMP expression and signalling, which correlate clinically with breast cancer progression. Ultimately a BMP profile could provide new prognostic disease markers. As the evidence suggests a role for BMPs in regulating breast tumour cellular function, in particular interactions with tumour stroma and the bone metastatic microenvironment, there may be novel therapeutic potential in targeting BMP signalling in breast cancer. This review provides an update on the current knowledge of BMP abnormalities and their implication in the development and progression of breast cancer, particularly in the disease-specific bone metastasis.

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Various Therapeutic Methods for the Treatment of Medication-Related Osteonecrosis of the Jaw (MRONJ) and Their Limitations: A Narrative Review on New Molecular and Cellular Therapeutic Approaches

Antioxidants ◽

10.3390/antiox10050680 ◽

2021 ◽

Vol 10 (5) ◽

pp. 680

Author(s):

Sung-Woon On ◽

Seoung-Won Cho ◽

Soo-Hwan Byun ◽

Byoung-Eun Yang

Keyword(s):

Bone Morphogenetic Proteins ◽

Maxillofacial Surgery ◽

Treatment Protocol ◽

Osteonecrosis Of The Jaw ◽

Therapeutic Modality ◽

Definitive Treatment ◽

Antiangiogenic Agents ◽

Platelet Concentrates ◽

Therapeutic Approaches ◽

Positive Effect

Medication-related osteonecrosis of the jaw (MRONJ) is one of the most interesting diseases in the field of maxillofacial surgery. In addition to bisphosphonates, the use of antiresorptive and antiangiogenic agents is known to be the leading cause. However, the exact pathogenesis of MRONJ has not been established, and various hypotheses have been proposed, such as oxidative stress-related theory. As a result, a definitive treatment protocol for MRONJ has not been identified, while various therapeutic approaches are applied to manage patients with MRONJ. Although the surgical approach to treat osteomyelitis of the jaw has been proven to be most effective, there are limitations, such as recurrence and delayed healing. Many studies and clinical trials are being conducted to develop another effective therapeutic modality. The use of some materials, including platelet concentrates and bone morphogenetic proteins, showed a positive effect on MRONJ. Among them, teriparatide is currently the most promising material, and it has shown encouraging results when applied to patients with MRONJ. Furthermore, cell therapy using mesenchymal stem cells showed promising results, and it can be the new therapeutic approach for the treatment of MRONJ. This review presents various treatment methods for MRONJ and their limitations while investigating newly developed and researched molecular and cellular therapeutic approaches along with a literature review.

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The Role of BMP Signaling in Osteoclast Regulation

Journal of Developmental Biology ◽

10.3390/jdb9030024 ◽

2021 ◽

Vol 9 (3) ◽

pp. 24

Author(s):

Brian Heubel ◽

Anja Nohe

Keyword(s):

Bone Formation ◽

Bone Morphogenetic Proteins ◽

Bone Diseases ◽

Bmp Signaling ◽

Bone Homeostasis ◽

Direct Stimulation ◽

Federal Drug Administration ◽

Bmp Pathway ◽

Stimulation Of

The osteogenic effects of Bone Morphogenetic Proteins (BMPs) were delineated in 1965 when Urist et al. showed that BMPs could induce ectopic bone formation. In subsequent decades, the effects of BMPs on bone formation and maintenance were established. BMPs induce proliferation in osteoprogenitor cells and increase mineralization activity in osteoblasts. The role of BMPs in bone homeostasis and repair led to the approval of BMP2 by the Federal Drug Administration (FDA) for anterior lumbar interbody fusion (ALIF) to increase the bone formation in the treated area. However, the use of BMP2 for treatment of degenerative bone diseases such as osteoporosis is still uncertain as patients treated with BMP2 results in the stimulation of not only osteoblast mineralization, but also osteoclast absorption, leading to early bone graft subsidence. The increase in absorption activity is the result of direct stimulation of osteoclasts by BMP2 working synergistically with the RANK signaling pathway. The dual effect of BMPs on bone resorption and mineralization highlights the essential role of BMP-signaling in bone homeostasis, making it a putative therapeutic target for diseases like osteoporosis. Before the BMP pathway can be utilized in the treatment of osteoporosis a better understanding of how BMP-signaling regulates osteoclasts must be established.

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Effects of bone morphogenetic proteins on epithelial repair

Experimental Biology and Medicine ◽

10.1177/15353702211028193 ◽

2021 ◽

pp. 153537022110281

Author(s):

Yu Hou ◽

Yu-Xi He ◽

Jia-Hao Zhang ◽

Shu-Rong Wang ◽

Yan Zhang

Keyword(s):

Growth Factors ◽

Epithelial Cells ◽

Bone Morphogenetic Proteins ◽

Epithelial Tissue ◽

Epithelial Repair ◽

Multiple Functions ◽

Epithelial Damage ◽

Damage Repair ◽

And Migration ◽

Proliferation And Migration

Epithelial tissue has important functions such as protection, secretion, and sensation. Epithelial damage is involved in various pathological processes. Bone morphogenetic proteins (BMPs) are a class of growth factors with multiple functions. They play important roles in epithelial cells, including in differentiation, proliferation, and migration during the repair of the epithelium. This article reviews the functions and mechanisms of the most profoundly studied BMPs in the process of epithelial damage repair and their clinical significance.

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Bone Morphogenetic Proteins and Diabetic Retinopathy

Biomolecules ◽

10.3390/biom11040593 ◽

2021 ◽

Vol 11 (4) ◽

pp. 593

Author(s):

Khaled Elmasry ◽

Samar Habib ◽

Mohamed Moustafa ◽

Mohamed Al-Shabrawey

Keyword(s):

Diabetic Retinopathy ◽

Bone Morphogenetic Proteins ◽

Potential Role ◽

Microvascular Dysfunction ◽

Cardiovascular Complications ◽

Bmp Signaling ◽

Age Related Macular Degeneration ◽

Age Related ◽

Retinal Inflammation ◽

Underlying Mechanisms

Bone morphogenetic proteins (BMPs) play an important role in bone formation and repair. Recent studies underscored their essential role in the normal development of several organs and vascular homeostasis in health and diseases. Elevated levels of BMPs have been linked to the development of cardiovascular complications of diabetes mellitus. However, their particular role in the pathogenesis of microvascular dysfunction associated with diabetic retinopathy (DR) is still under-investigated. Accumulated evidence from our and others’ studies suggests the involvement of BMP signaling in retinal inflammation, hyperpermeability and pathological neovascularization in DR and age-related macular degeneration (AMD). Therefore, targeting BMP signaling in diabetes is proposed as a potential therapeutic strategy to halt the development of microvascular dysfunction in retinal diseases, particularly in DR. The goal of this review article is to discuss the biological functions of BMPs, their underlying mechanisms and their potential role in the pathogenesis of DR in particular.

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Bone Morphogenetic Proteins, Carriers, and Animal Models in the Development of Novel Bone Regenerative Therapies

Materials ◽

10.3390/ma14133513 ◽

2021 ◽

Vol 14 (13) ◽

pp. 3513

Author(s):

Nikola Stokovic ◽

Natalia Ivanjko ◽

Drazen Maticic ◽

Frank P. Luyten ◽

Slobodan Vukicevic

Keyword(s):

Animal Models ◽

Bone Formation ◽

Bone Morphogenetic Proteins ◽

Animal Experiments ◽

Inorganic Materials ◽

New Bone Formation ◽

Segmental Bone ◽

Posterolateral Spinal Fusion ◽

Regenerative Therapies ◽

Observation Period

Bone morphogenetic proteins (BMPs) possess a unique ability to induce new bone formation. Numerous preclinical studies have been conducted to develop novel, BMP-based osteoinductive devices for the management of segmental bone defects and posterolateral spinal fusion (PLF). In these studies, BMPs were combined with a broad range of carriers (natural and synthetic polymers, inorganic materials, and their combinations) and tested in various models in mice, rats, rabbits, dogs, sheep, and non-human primates. In this review, we summarized bone regeneration strategies and animal models used for the initial, intermediate, and advanced evaluation of promising therapeutical solutions for new bone formation and repair. Moreover, in this review, we discuss basic aspects to be considered when planning animal experiments, including anatomical characteristics of the species used, appropriate BMP dosing, duration of the observation period, and sample size.

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