The many ways of osteoclast activation

Lorenzo, Joseph

doi:10.1172/jci94606

Cited by 114 publications

(84 citation statements)

References 21 publications

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“…For decades studies of RANK have been focusing on osteoclastogenesis. 19 , 20 And RANKL inhibitor denosumab has been used clinically to inhibit osteoclastogenesis as an anti-resorptive agent. 9 …”

Section: Discussionmentioning

confidence: 99%

RANKL signaling in bone marrow mesenchymal stem cells negatively regulates osteoblastic bone formation

et al. 2018

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RANKL signaling is essential for osteoclastogenesis. Its role in osteoblastic differentiation and bone formation is unknown. Here we demonstrate that RANK is expressed at an early stage of bone marrow mesenchymal stem cells (BMSCs) during osteogenic differentiation in both mice and human and decreased rapidly. RANKL signaling inhibits osteogenesis by promoting β-catenin degradation and inhibiting its synthesis. In contrast, RANKL signaling has no significant effects on adipogenesis of BMSCs. Interestingly, conditional knockout of rank in BMSCs with Prx1-Cre mice leads to a higher bone mass and increased trabecular bone formation independent of osteoclasts. In addition, rankflox/flox: Prx1-Cre mice show resistance to ovariectomy-(OVX) induced bone loss. Thus, our results reveal that RANKL signaling regulates both osteoclasts and osteoblasts by inhibition of osteogenic differentiation of BMSCs and promotion of osteoclastogenesis.

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Section: Discussionmentioning

confidence: 99%

RANKL signaling in bone marrow mesenchymal stem cells negatively regulates osteoblastic bone formation

et al. 2018

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“…To our knowledge, imbalance of skeletal homeostasis, an active coupling process that occurs via bone formation and bone resorption, results in osteoporosis (Hendrickx, Boudin, & Van Hul, ). To date, multifarious signaling pathways and critical molecules have been digged out to explore the mechanism of osteoporosis, like canonical Wnt/β‐catenin pathway (Baron & Kneissel, ; Canalis, ; Lerner & Ohlsson, ) and RANKL/RANK pathway (Crockett, Mellis, Scott, & Helfrich, ; Lorenzo, ; Luo, Ren, Li, Lian, & Lin, ). However, the detailed pathogenesis of osteoporosis remains elusive.…”

Section: Introductionmentioning

confidence: 99%

Mammalian target of rapamycin as a therapeutic target in osteoporosis

Shen

Ren²,

Qiu

et al. 2017

Journal Cellular Physiology

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The mechanistic target of rapamycin (mTOR) plays a key role in sensing and integrating large amounts of environmental cues to regulate organismal growth, homeostasis, and many major cellular processes. Recently, mounting evidences highlight its roles in regulating bone homeostasis, which sheds light on the pathogenesis of osteoporosis. The activation/inhibition of mTOR signaling is reported to positively/negatively regulate bone marrow mesenchymal stem cells (BMSCs)/osteoblasts-mediated bone formation, adipogenic differentiation, osteocytes homeostasis, and osteoclasts-mediated bone resorption, which result in the changes of bone homeostasis, thereby resulting in or protect against osteoporosis. Given the likely importance of mTOR signaling in the pathogenesis of osteoporosis, here we discuss the detailed mechanisms in mTOR machinery and its association with osteoporosis therapy.

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“…TRAP staining suggested that the osteoclast number in the tibia with loading is significantly fewer than that in the nonloading group. Genes such as NFATc1, RANKL, and cathepsin K are important for osteoclast development (23,(47)(48)(49). The result of this study indicated that ankle loading suppressed activity of osteoclasts by regulating NFATc1, RANKL, cathepsin K. In addition, bone formation in the tibia was promoted by ankle loading with an increase in the number of osteoblasts.…”

Section: Discussionmentioning

confidence: 72%

Ankle loading ameliorates bone loss from breast cancer–associated bone metastasis

et al. 2019

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Breast cancer is a serious health problem that preferentially metastasizes to bone. We have previously shown that bone loss can be prevented by mechanical loading, but the efficacy of ankle loading for metastasis‐linked bone loss has not been investigated. This study showed that body weight was decreased after inoculation of tumor cells, but ankle loading restored a rapid weight loss. The nonloading group exhibited a decrease in bone volume/tissue volume (BV/TV), trabecular thickness, and trabecular number (all P < 0.01) as well as an increase in trabecular separation (P < 0.001). However, ankle loading improved those changes (all P < 0.05). Furthermore, although the nonloading group increased the tumor bearing as well as expression of IL‐8 and matrix metalloproteinase 9, ankle loading decreased them. Induction of tumor in the bone elevated the osteoclast number (P < 0.05) as well as the levels of nuclear factor of activated T‐cells cytoplasmic 1, NF‐κB ligand, cathepsin K, and serum tartrate‐resistant acid phosphatase type 5b, but ankle loading reduced osteoclast activity and those levels (all P < 0.05). Tumor bearing was positively correlated with the osteoclast number (P < 0.01) and negatively correlated with BV/TV and the osteoblast number (both P < 0.01). Collectively, these findings demonstrate that ankle loading suppresses tumor growth and osteolysis by inhibiting bone resorption and enhancing bone formation.—Yang, S., Liu, H., Zhu, L., Li, X., Liu, D., Song, X., Yokota, H., Zhang, P. Ankle loading ameliorates bone loss from breast cancer–associated bone metastasis. FASEB J. 33, 10742–10752 (2019). http://www.fasebj.org

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The many ways of osteoclast activation

Cited by 114 publications

References 21 publications

RANKL signaling in bone marrow mesenchymal stem cells negatively regulates osteoblastic bone formation

RANKL signaling in bone marrow mesenchymal stem cells negatively regulates osteoblastic bone formation

Mammalian target of rapamycin as a therapeutic target in osteoporosis

Ankle loading ameliorates bone loss from breast cancer–associated bone metastasis

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