Wnt3a involved in the mechanical loading on improvement of bone remodeling and angiogenesis in a postmenopausal osteoporosis mouse model

Li, Xinle; Liu, Daquan; Li, Jie; Yang, Shuang; Xu, Jinfeng; Yokota, Hiroki; Zhang, Ping

doi:10.1096/fj.201802711r

Cited by 41 publications

(53 citation statements)

References 60 publications

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“…In vivo experiments showed that mechanical loading reduces the number of osteoclasts, and molecular experiments revealed that the expression of osteoclast-related factors decreases after mechanical loading. In vitro analysis confirmed that mechanical loading inhibited differentiation, migration, and adhesion of osteoclasts (22,23,40). Our previous study showed that responsiveness to ankle loading differs in the periosteum and endosteum.…”

Section: Discussionsupporting

confidence: 63%

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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Section: Discussionsupporting

confidence: 63%

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

et al. 2019

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“…The ratio between length of TRAP-positive cells and total circumference of bone trabecula was calculated. 23 It represented the activity of osteoclast. MacNeal's staining was used for identifying osteoblasts as described previously.…”

Section: Histology Trap Macneal's and Immunohistochemistry Assaysmentioning

confidence: 99%

“…Javaheri et al showed that mice with a heterozygous deletion of β‐catenin in osteocytes lose the ability to form new bone in response to mechanical loading . Furthermore, our previous experiments showed that knee loading could inhibit osteoclast development by regulating Wnt signaling and be used to treat early OA, Wnt3a plays a key role in the treatment of OP in response to knee loading . However, whether knee loading also plays a role in OPOA by regulating Wnt signal is unknown.…”

Section: Introductionmentioning

confidence: 99%

Knee loading repairs osteoporotic osteoarthritis by relieving abnormal remodeling of subchondral bone via Wnt/β‐catenin signaling

Zheng

Ding

et al. 2020

FASEB j.

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Osteoporotic osteoarthritis (OPOA) is a common bone disease mostly in the elderly, but the relationship between Osteoporotic (OP) and osteoarthritis (OA) is complex. It has been shown that knee loading can mitigate OA symptoms. However, its effects on OPOA remain unclear. In this study, we characterized pathological linkage of OP to OA, and evaluated the effect of knee loading on OPOA. We employed two mouse models (OA and OPOA), and conducted histology, cytology, and molecular analyses. In the OA and OPOA groups, articular cartilage was degenerated and Osteoarthritis Research Society International score was increased. Subchondral bone underwent abnormal remodeling, the differentiation of bone marrow mesenchymal stem cells (BMSCs) to osteoblasts and chondrocytes was reduced, and migration and adhesion of pre‐osteoclasts were enhanced. Compared to the OA group, the pathological changes of OA in the OPOA group were considerably aggravated. After knee loading, however, cartilage degradation was effectively prevented, and the abnormal remodeling of subchondral bone was significantly inhibited. The differentiation of BMSCs was also improved, and the expression of Wnt/β‐catenin was elevated. Collectively, this study demonstrates that osteoporosis aggravates OA symptoms. Knee loading restores OPOA by regulating subchondral bone remodeling, and may provide an effective method for repairing OPOA.

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“…Osteoporosis was caused by many factors and is characteristic of the decreased bone mineral density (BMD) and the deteriorated microarchitecture of bone and thereby increasing the incidence of fracture (Li et al, 2019). Osteoporosis is divided into two categories: primary osteoporosis and secondary osteoporosis.…”

Section: Introductionmentioning

confidence: 99%

“…In addition, a monoclonal antibody against RANKL is proved to be highly effective in blocking bone resorption and leads to development of a drug denosumab that successful reduces fractures, which is now one of the therapeutic options for osteoporosis treatment (Solling, Harslof, & Langdahl, 2018). However, more and more attention has been paid to the abnormalities of bone metabolism and related diseases caused by the activity or differentiation abnormalities of osteoblast (Li et al, 2019; Son, Lee, Lee, Lee, & Oh, 2019). The balance between osteoblast proliferation and apoptosis determines the number of active osteoblasts, thereby affecting bone formation homeostasis.…”

Section: Introductionmentioning

confidence: 99%

PSMC6 promotes osteoblast apoptosis through inhibiting PI3K/AKT signaling pathway activation in ovariectomy‐induced osteoporosis mouse model

Zhang

Cao

et al. 2020

Journal Cellular Physiology

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There is now increasing evidence which suggests a key role for osteoblast apoptosis in the pathogenesis of postmenopausal osteoporosis. Here, we evaluated the role and mechanism of proteasome 26S subunit, ATPase (PSMC) 6, a protein that is highly expressed in bone. Gene expression pattern had been extracted based on database of Gene Expression Omnibus (GEO). GEO2R was employed for analyses, while the DAVID database was adopted to further analyze the gene ontology (GO) as well as Kyoto Encyclopedia of Genomes pathway (KEGG) enrichment. Then, the Search Tool Retrieval of Interacting Genes (STRING) was utilized to carry out interaction regulatory network for the top 200 differentially expressed genes (DEGs). A key gene, called PSMC6, was identified by Cytoscape 3.6.0. The OVX osteoporosis model was established in female C57BL/6 mice by full bilateral ovariectomy. According to our findings, PSMC6 gene knockout would elevate bone mineral density (BMD) and the phosphorylation level of PI3K protein and increased the protein level of cleaved caspase‐3/‐9 in OVX osteoporosis mice. Further, MTT, bromodeoxyuridine, and flow cytometry assays revealed that PSMC6 inhibition promoted the progression of cell cycle and cell proliferation, whereas, PSMC6 overexpression promoted the apoptosis and inhibited cell cycle progression and cell proliferation in vitro. Besides, we found that PI3K activation significantly decreased PSMC6‐induced osteoblast apoptosis and promoted cell proliferation through regulating the protein levels of p53, cyclinD1, and cleaved caspase‐3/9. In conclusion, PSMC6 aggravated the degree of OVX‐induced osteoporosis by inhibiting the PI3K/AKT signal transduction pathway, thereby promoting the apoptosis of osteoblasts.

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Wnt3a involved in the mechanical loading on improvement of bone remodeling and angiogenesis in a postmenopausal osteoporosis mouse model

Cited by 41 publications

References 60 publications

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

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

Knee loading repairs osteoporotic osteoarthritis by relieving abnormal remodeling of subchondral bone via Wnt/β‐catenin signaling

PSMC6 promotes osteoblast apoptosis through inhibiting PI3K/AKT signaling pathway activation in ovariectomy‐induced osteoporosis mouse model

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