Bone regeneration in osteoporosis: opportunities and challenges

Patel, Dhrumi; Wairkar, Sarika

doi:10.1007/s13346-022-01222-6

Cited by 25 publications

(11 citation statements)

References 106 publications

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“…Fer‐1 and DFO can not only inhibit ferroptosis but also suppress the release and cytotoxicity of TNF‐α. Antiresorptive agents like bisphosphonates are the most commonly used drugs for osteoporosis, which cause varieties of adverse effects and fail to provide curative treatment 83 . Bone regenerative therapy has been recently developed and become a potential strategy to overcome the limitations of conventional therapy 83 .…”

Section: Discussionmentioning

confidence: 99%

“…Antiresorptive agents like bisphosphonates are the most commonly used drugs for osteoporosis, which cause varieties of adverse effects and fail to provide curative treatment. 83 Bone regenerative therapy has been recently developed and become a potential strategy to overcome the limitations of conventional therapy. 83 In our study, we found that Fer-1 and DFO can effectively support bone regeneration through increasing the abundance of type H vessels and osteoprogenitors.…”

Section: Discussionmentioning

confidence: 99%

“…83 Bone regenerative therapy has been recently developed and become a potential strategy to overcome the limitations of conventional therapy. 83 In our study, we found that Fer-1 and DFO can effectively support bone regeneration through increasing the abundance of type H vessels and osteoprogenitors. Moreover, Fer-1 and DFO have proven effective to treat obesity-related liver and kidney diseases.…”

Section: Discussionmentioning

confidence: 99%

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Interaction between ferroptosis and TNF‐α: Impact in obesity‐related osteoporosis

Chen

Liu

et al. 2023

The FASEB Journal

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The relationship of obesity and osteoporosis has been widely studied over the past years. However, the implications of obesity for bone health remain controversial, and the underlying molecular mechanism is not yet fully understood.This study demonstrated that high-fat diet-induced obesity leads to significantly decreased bone volume/tissue volume (BV/TV), trabecular number (Tb.N), and cortical thickness (Ct.Th) of male rat femur after mechanical loading effects of body weight were controlled. HFD-induced obese rats exhibited attenuated expression of ferroptosis inhibitory protein SLC7A11 and GPX4 in bone tissues, which was correlated with elevated serum TNF-α concentration. Ferroptosis inhibitor administration could effectively rescue decreased osteogenesis-associated type H vessels and osteoprogenitors, and downregulate serum levels of TNF-α to ameliorate bone loss in obese rats. Since ferroptosis and TNF-α both affect bone and vessel formation, we further investigated the interaction between ferroptosis and TNF-α, and its impact in osteogenesis and angiogenesis in vitro. In human osteoblast-like MG63 and umbilical vein endothelial cells (HUVEC), TNF-α/ TNFR2 signaling promoted cystine uptake and GSH biosynthesis to provide protection against low-dose ferroptosis inducer erastin. While, TNF-α/TNFR1 facilitated ferroptosis in the presence of high-dose erastin through ROS accumulation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Interaction between ferroptosis and TNF‐α: Impact in obesity‐related osteoporosis

Chen

Liu

et al. 2023

The FASEB Journal

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“…It is desirable to prevent fracture through impeding bone resorption cascade which could be combined with facilitation of bone regeneration [19]. Examples of therapeutic agents that can aid in bone regeneration include teriparatide (Forteo®), and hormone replacement therapy with estrogen, calcitonin, and bisphosphonates [20,21]. However, there are limitations surrounding the routine use of these products, such as high cost, poor compliance, risks, and side effects, mixed results, and poor pharmacokinetic profile without other modulating agents [22].…”

Section: Introductionmentioning

confidence: 99%

Efficacy assessment of methylcellulose-based thermoresponsive hydrogels loaded with gallium acetylacetonate in osteoclastic bone resorption

Ghanta

Winschel

Hessel

et al. 2023

Drug Deliv. and Transl. Res.

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Homeostatic imbalance involving progressive stimulation of osteoclast (OC) differentiation and function will lead to an increased risk of fragility fractures. In this regard, we investigated gallium acetylacetonate (GaAcAc) as a possible treatment for osteoclastic bone resorption. Further, the extent to which suitable delivery systems can enhance the therapeutic potential of GaAcAc was evaluated. GaAcAc solution (10–50 µg/mL) suppressed OC differentiation using murine monocytic RAW 264.7 or hematopoietic stem cells. Methylcellulose-based hydrogels were fabricated and characterized based on biocompatibility with bone cells, GaAcAc loading, and thermoresponsive behavior using storage (G′) and loss (G″) moduli parameters. Compared to GaAcAc solution, hydrogels loaded with GaAcAc (GaMH) were more effective in suppressing OC differentiation and function. The number and extent of bone resorption pits from ex vivo studies were markedly reduced with GaMH treatment. Mechanistic assessment of GaMH efficacy showed superiority, compared to GaAcAc solution, in downregulating the expression of key markers involved in mediating OC differentiation (such as NFAT2, cFos, TRAF6, and TRAP) as well as in bone resorption by OCs (cathepsin K or CTSK). Additional studies (in vitro and in vivo) suggested that the performance of GaMH could be ascribed to controlled release of GaAcAc and the ability to achieve prolonged bio-retention after injection in BALB/c mice, which plausibly maximized the therapeutic impact of GaAcAc. Overall, the work demonstrated, for the first time, the therapeutic efficacy of GaAcAc and the therapeutic potential of GaMH delivery systems in osteoclastic bone resorption. Graphical Abstract "Image missing"

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“…Because of the aging of the global population, the incidence of this disease is expected to increase. Osteoporosis is characterized by decreased bone mineral density (BMD) and an increased risk of bone fragility, often causing chronic pain, fracture, and disability, resulting in impaired quality of life 3 . Postmenopausal osteoporosis, also known as type I primary osteoporosis, is caused by estrogen deficiency and is the major type of osteoporosis 4 .…”

mentioning

confidence: 99%

Association of hormone preparations with bone mineral density, osteopenia, and osteoporosis in postmenopausal women: data from National Health and Nutrition Examination Survey 1999-2018

Sun

2023

Menopause

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Bone regeneration in osteoporosis: opportunities and challenges

Cited by 25 publications

References 106 publications

Interaction between ferroptosis and TNF‐α: Impact in obesity‐related osteoporosis

Interaction between ferroptosis and TNF‐α: Impact in obesity‐related osteoporosis

Efficacy assessment of methylcellulose-based thermoresponsive hydrogels loaded with gallium acetylacetonate in osteoclastic bone resorption

Association of hormone preparations with bone mineral density, osteopenia, and osteoporosis in postmenopausal women: data from National Health and Nutrition Examination Survey 1999-2018

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