Antiresorptive agents and osteoclast apoptosis

Stern, Paula H.

doi:10.1002/jcb.21311

Cited by 31 publications

(27 citation statements)

References 87 publications

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“…Regulation of bone cell apoptosis holds important therapeutic value for the treatment of osteopenic diseases including periodontitis, postmenopausal osteoporosis, glucocorticoid-induced osteoporosis, rheumatoid arthritis, and metastatic tumor-driven osteolysis [1,2,27], in which increase of OC activity results in a net decrease in bone mass. Therefore, molecules involved in the promoting OC apoptosis and suppression of OC activity provide us good therapeutic tools for such pathologic conditions.…”

Section: Discussionmentioning

confidence: 99%

Human osteoclasts differentiated from umbilical cord blood precursors are less prone to apoptotic stimuli than osteoclasts from peripheral blood

et al. 2008

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Osteoclasts (OCs) are specialized bone-resorbing cells. For "in vitro" analysis, they may be obtained from the precursors present in peripheral blood (PB) or umbilical cord blood (UCB), but there has been no detailed analysis of how the kind of source and cell culture conditions may affect the behavior of these cells. Here we analyzed the behavior of OCs after transfection with specific transcription factor decoy molecules founding that the OCs from PB undergo apoptosis when nuclear factor kappa B (NF-kB) or NFATc1 were removed, or when ERalpha expression was increased. Conversely, OCs from UCB showed a strong resistance to apoptotic stimuli. We found that survival signals including Bcl-2, Bcl-XL, and Survivin are present in the OCs/UCB, but not in OCs/PB. The resistance to apoptosis seems to be not correlated with NF-kB, NFATc1, or ERalpha expression level, or with the activation of ERK and Akt proteins. One of the mechanisms responsible for bone remodeling is apoptosis, and being susceptible of therapeutic manipulation, the OCs are extensively employed to investigate cell response to therapies for the treatment of bone loss associated with several diseases, including periodontitis, osteoporosis, and metastatic osteolysis. Therefore, our evidences are to be taken in consideration when both the effects of biological modifiers are tested and OCs apoptosis molecular mechanisms are investigated.

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Section: Discussionmentioning

confidence: 99%

Human osteoclasts differentiated from umbilical cord blood precursors are less prone to apoptotic stimuli than osteoclasts from peripheral blood

et al. 2008

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“…Importantly, the approach to reduce the bone resorptive activity of mature osteoclasts via decreasing the expression/ activity of signaling molecules required for the apoptosis and/or survival of mature osteoclasts has been suggested to be one of the strategies to inhibit osteoclast-mediated bone loss (Stern, 2007). Since the possibility that apoptosis is involved in the inhibitory action of saurolactam on bone resorption could not be excluded in this study, we further evaluated the effect of saurolactam on the induction of apoptosis in mature osteoclasts.…”

Section: Journal Of Cellular Physiology a N T I -R E S O R P T I V E mentioning

confidence: 99%

“…M P < 0.05; Because apoptosis is characterized by activation of a caspase cascade that can be induced by the release of cytochrome c (Hengartner, 2000;Stern, 2007), we evaluated the effect of saurolactam on caspase-3 activation and cytochrome c release in mature osteoclasts derived from RAW264.7 cells. When mature osteoclasts were incubated with saurolactam before incubation with RANKL for 4 or 24 h, caspase-3 activity was significantly induced by saurolactam at high concentrations (!9 mM; Fig.…”

Section: Fig 4 Effect Of Saurolactam On Rankl R M-csf-induced Trap mentioning

confidence: 99%

Saurolactam inhibits osteoclast differentiation and stimulates apoptosis of mature osteoclasts

Kim

Ryu

Choi

et al. 2009

Journal Cellular Physiology

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The receptor activator of nuclear factor-kappaB ligand (RANKL) plays a critical role in the differentiation and bone resorptive activity of osteoclasts. Recently, the development of anti-resorptive agents from natural substances has become a subject of interest. Therefore, we evaluated the effects of 222 natural compounds on the RANKL-induced tartrate-resistance acid phosphatase (TRAP; a marker for osteoclast differentiation) activity and multinucleated osteoclast formation in RAW264.7 murine macrophage cells. We found that saurolactam was one of the compounds inhibiting the RANKL-induced osteoclastogenesis; it significantly inhibited the RANKL-induced TRAP activity and formation of multinucleated osteoclasts without any cytotoxicity. Interestingly, saurolactam prevented RANKL-induced activation of MAP kinases and NF-kappaB, and mRNA expression of osteoclast-related genes and transcription factors (c-Fos, Fra-2, and NFATc1). We also observed the inhibitory effect of saurolactam on the differentiation of mouse bone marrow-derived macrophages into osteoclasts. Furthermore, saurolactam inhibited the bone resorptive activity of mature osteoclasts with the induction of apoptotic signaling cascade and the inhibition of survival signaling pathways such as c-Src/PI3K/Akt, Ras/ERK, and JNK/c-Jun. In conclusion, although further studies are needed to determine the precise mechanism and biological efficacy of saurolactam in osteoclast-mediated bone disorders, our results demonstrate that saurolactam potentially inhibits osteoclast differentiation by preventing the activation of MAP kinases and transcription factors that consequently affect the regulation of genes required for osteoclastogenesis, and the bone resorptive activity of mature osteoclasts by inhibiting osteoclast survival-related signaling pathways and triggering the apoptotic signaling cascade.

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“…Non N-BPs inhibit the conversion of ATP to ADP which causes mitochondrial dysfunction leading to apoptosis. N-BPs alter protein prenylation by inhibiting farnesyldiphosphonate (FPP) synthase which is important for the mevalonate pathway in eukaryotic cells (Green, 2002;Luckman et al, 1998;Monkkonen et al, 2006;Moreau et al, 2007;Stern, 2007).…”

Section: Bisphosphonates As Therapeutic Modalitiesmentioning

confidence: 99%

Are Macrophages in Tumors Good Targets for Novel Therapeutic Approaches?

Alahari¹,

Dong²

2015

Molecules and Cells

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The development of cancer has been an extensively researched topic over the past few decades. Although great strides have been made in cancer prevention, diagnosis, and treatment, there is still much to be learned about cancer's micro-environmental mechanisms that contribute to cancer formation and aggressiveness. Macrophages, lymphocytes which originate from monocytes, are involved in the inflammatory response and often dispersed to areas of infection to fight harmful antigens and mutated cells in tissues. Macrophages have a plethora of roles including tissue development and repair, immune system functions, and inflammation. We discuss various pathways by which macrophages get activated, various approaches that can regulate the function of macrophages, and how these approaches can be helpful in developing new cancer therapies.

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Antiresorptive agents and osteoclast apoptosis

Cited by 31 publications

References 87 publications

Human osteoclasts differentiated from umbilical cord blood precursors are less prone to apoptotic stimuli than osteoclasts from peripheral blood

Human osteoclasts differentiated from umbilical cord blood precursors are less prone to apoptotic stimuli than osteoclasts from peripheral blood

Saurolactam inhibits osteoclast differentiation and stimulates apoptosis of mature osteoclasts

Are Macrophages in Tumors Good Targets for Novel Therapeutic Approaches?

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