Bortezomib enhances the osteogenic differentiation capacity of human mesenchymal stromal cells derived from bone marrow and placental tissues

Sanvoranart, Tanwarat; Supokawej, Aungkura; Kheolamai, Pakpoom; U-Pratya, Yaowalak; Klincumhom, Nuttha; Manochantr, Sirikul; Wattanapanitch, Methichit; Issaragrisil, Surapol

doi:10.1016/j.bbrc.2014.04.044

Cited by 18 publications

(22 citation statements)

References 28 publications

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“…Bortezomib also increases osterix, vitamin D receptor signaling, and Gli-3 [58–61] and by inhibition of DKK-1 expression [50,51] and fibroblast growth factor 2-induced reduction of transcriptional coactivator with PDZ-binding motif levels in osteoblast-like cells [62]. Bortezomib treatment also enhances the osteogenic differentiation capacity of mesenchymal stromal cells, which have the ability to differentiate into osteoblasts and possibly regulate E3 ubiquitin ligase Smurf1 (Smad ubiquitin regulatory factor 1) degradation [60,63–64]. …”

Section: Proteasome Inhibitors and Bone Remodeling In MMmentioning

confidence: 99%

“…In terms of bone-anabolic activity, carfilzomib and oprozomib promote the differentiation of osteoblasts from mesenchymal stem cells (similar to bortezomib) [63], and increase matrix mineralization and calcium deposition in vitro [81]. Carfilzomib induces osteoblast differentiation via Wnt-dependent activation of the β-catenin/T-cell factor pathway [82] and stimulates osteogenesis via inhibition of the notch1 receptor (part of the Notch signaling pathway) [83].…”

Section: Proteasome Inhibitors and Bone Remodeling In MMmentioning

confidence: 99%

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The effects of proteasome inhibitors on bone remodeling in multiple myeloma

Zangari

Suva

2016

Bone

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Bone disease is a characteristic feature of multiple myeloma, a malignant plasma cell dyscrasia. In patients with multiple myeloma, the normal process of bone remodeling is dysregulated by aberrant bone marrow plasma cells, resulting in increased bone resorption, prevention of new bone formation, and consequent bone destruction. The ubiquitin–proteasome system, which is hyperactive in patients with multiple myeloma, controls the catabolism of several proteins that regulate bone remodeling. Clinical studies have reported that treatment with the first-in-class proteasome inhibitor bortezomib reduces bone resorption and increases bone formation and bone mineral density in patients with multiple myeloma. Since the introduction of bortezomib in 2003, several next-generation proteasome inhibitors have also been used clinically, including carfilzomib, oprozomib, ixazomib, and delanzomib. This review summarizes the available preclinical and clinical evidence regarding the effect of proteasome inhibitors on bone remodeling in multiple myeloma.

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Section: Proteasome Inhibitors and Bone Remodeling In MMmentioning

confidence: 99%

Section: Proteasome Inhibitors and Bone Remodeling In MMmentioning

confidence: 99%

The effects of proteasome inhibitors on bone remodeling in multiple myeloma

Zangari

Suva

2016

Bone

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“…Recently, it was shown that very low doses of bortezomib (less than 5 nM) can induce osteogenic differentiation of murine MSCs derived from bone marrow and placental tissues and upregulate osteogenic marker genes . This dose is 200‐ to 300‐folds lower than the concentration used to treat MM .…”

Section: Other Peptidesmentioning

confidence: 99%

Short Anabolic Peptides for Bone Growth

Amso

Cornish²,

Brimble

2016

Medicinal Research Reviews

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Loss of bone occurs in the age-related skeletal disorder, osteoporosis, leading to bone fragility and increased incidence of fractures, which are associated with enormous costs and substantial morbidity and mortality. Recent data indicate that osteoporotic fractures are more common than other diseases, which usually attract public attention (e.g., heart attack and breast cancer). The prevention and treatment of this skeletal disorder are therefore of paramount importance. Majority of osteoporosis medications restore skeletal balance by reducing osteoclastic activity, thereby reducing bone resorption. These agents, however, do not regenerate damaged bone tissue, leaving limited options for patients once bone loss has occurred. Recently, attention has turned to bone-anabolic agents. Such agents have the ability to increase bone mass and strength, potentially reversing structural damage. To date, only one bone-anabolic drug is available in the market. The discovery of more novel, cost-effective bone anabolic agents is therefore a priority to treat those suffering from this disabling condition. Short peptides offer an important alternative for the development of novel bone-anabolic agents given their high target binding specificity, which translates into potent activity with limited side effects. This review summarizes attempts in the identification of bone-anabolic peptides, and their development for promoting bone growth.

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“…Placenta-derived MSCs (PL-MSCs) express common markers of MSCs and exhibit adipogenic, osteogenic, and neurogenic differentiation capacities [139]. Sanvoranart et al demonstrated that PL-MSCs responded to bortezomib, a chemotherapeutic agent that improves osteolytic lesions in multiple myeloma, via enhancement of osteogenic differentiation, similarly to BM-MSCs [140]. This finding suggests the potential therapeutic application of PL-MSCs in osteopenia and osteoporosis patients.…”

Section: Introductionmentioning

confidence: 99%

Osteoporosis: the current status of mesenchymal stem cell-based therapy

et al. 2016

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Osteoporosis, or bone loss, is a progressive, systemic skeletal disease that affects millions of people worldwide. Osteoporosis is generally age related, and it is underdiagnosed because it remains asymptomatic for several years until the development of fractures that confine daily life activities, particularly in elderly people. Most patients with osteoporotic fractures become bedridden and are in a life-threatening state. The consequences of fracture can be devastating, leading to substantial morbidity and mortality of the patients. The normal physiologic process of bone remodeling involves a balance between bone resorption and bone formation during early adulthood. In osteoporosis, this process becomes imbalanced, resulting in gradual losses of bone mass and density due to enhanced bone resorption and/or inadequate bone formation. Several growth factors underlying age-related osteoporosis and their signaling pathways have been identified, such as osteoprotegerin (OPG)/receptor activator of nuclear factor B (RANK)/RANK ligand (RANKL), bone morphogenetic protein (BMP), wingless-type MMTV integration site family (Wnt) proteins and signaling through parathyroid hormone receptors. In addition, the pathogenesis of osteoporosis has been connected to genetics. The current treatment of osteoporosis predominantly consists of antiresorptive and anabolic agents; however, the serious adverse effects of using these drugs are of concern. Cell-based replacement therapy via the use of mesenchymal stem cells (MSCs) may become one of the strategies for osteoporosis treatment in the future.

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Bortezomib enhances the osteogenic differentiation capacity of human mesenchymal stromal cells derived from bone marrow and placental tissues

Cited by 18 publications

References 28 publications

The effects of proteasome inhibitors on bone remodeling in multiple myeloma

The effects of proteasome inhibitors on bone remodeling in multiple myeloma

Short Anabolic Peptides for Bone Growth

Osteoporosis: the current status of mesenchymal stem cell-based therapy

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