The role of CKIP-1 in osteoporosis development and treatment

Peng, Xiaoxia; Wu, Xuejun; Zhang, J.; Zhang, Ge; Li, Gang; Pan, Xinghua

doi:10.1302/2046-3758.72.bjr-2017-0172.r1

Cited by 31 publications

(20 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recent studies demonstrate that CK2 interacting protein-1 (CKIP-1) plays an important role in the progression of osteoporosis [ 92 ]. Additionally, the CK2 inhibitor CX-4945 has been shown to promote osteoblastogenesis and inhibit osteoclastogenesis [ 93 ].…”

Section: Discussionmentioning

confidence: 99%

A Synthetic Peptide, CK2.3, Inhibits RANKL-Induced Osteoclastogenesis through BMPRIa and ERK Signaling Pathway

Nguyen

Kelly

Wood

et al. 2020

JDB

View full text Add to dashboard Cite

The skeletal system plays an important role in the development and maturation process. Through the bone remodeling process, 10% of the skeletal system is renewed every year. Osteoblasts and osteoclasts are two major bone cells that are involved in the development of the skeletal system, and their activity is kept in balance. An imbalance between their activities can lead to diseases such as osteoporosis that are characterized by significant bone loss due to the overactivity of bone-resorbing osteoclasts. Our laboratory has developed a novel peptide, CK2.3, which works as both an anabolic and anti-resorptive agent to induce bone formation and prevent bone loss. We previously reported that CK2.3 mediated mineralization and osteoblast development through the SMAD, ERK, and AKT signaling pathways. In this study, we demonstrated the mechanism by which CK2.3 inhibits osteoclast development. We showed that the inhibition of MEK by the U0126 inhibitor rescued the osteoclast development of RAW264.7 induced by RANKL in a co-culture system with CK2.3. We observed that CK2.3 induced ERK activation and BMPRIa expression on Day 1 after stimulation with CK2.3. While CK2.3 was previously reported to induce the SMAD signaling pathway in osteoblast development, we did not observe any changes in SMAD activation in osteoclast development with CK2.3 stimulation. Understanding the mechanism by which CK2.3 inhibits osteoclast development will allow CK2.3 to be developed as a new treatment for osteoporosis.

show abstract

Section: Discussionmentioning

confidence: 99%

A Synthetic Peptide, CK2.3, Inhibits RANKL-Induced Osteoclastogenesis through BMPRIa and ERK Signaling Pathway

Nguyen

Kelly

Wood

et al. 2020

JDB

View full text Add to dashboard Cite

show abstract

“…However, CKIP-1 inhibits both osteogenesis and adipogenesis via distinct mechanisms. [ 21 ] Previous studies have shown that CKIP-1 inhibits osteogenesis and osteoprecursor cells through Smurf1 ligase-mediated degradation of Smad1/5 and mitogen-activated protein kinase kinase 2. [ 8 , 22 ] In adipogenic differentiation, CKIP-1 interacts with the histone deacetylase 1 in the nucleus and inhibits the transcription of CCAAT/enhancer-binding protein α, which is a crucial adipogenic transcription factor.…”

Section: Discussionmentioning

confidence: 99%

Inflammation-mediated age-dependent effects of casein kinase 2-interacting protein-1 on osteogenesis in mesenchymal stem cells

Tian

Gong

et al. 2020

Chinese Medical Journal

View full text Add to dashboard Cite

Background The casein kinase 2-interacting protein-1 ( CKIP-1 ) is important in the development of osteoblasts and cardiomyocytes. However, the effects of CKIP-1 on osteoblast precursor mesenchymal stem cells (MSCs) remain unclear. This study aimed to determine whether CKIP-1 affects osteogenic differentiation in MSCs and explore the relationship of CKIP-1 and inflammation. Methods Bone marrow MSCs of CKIP-1 wild type (WT) and knockout (KO) mice were cultivated in vitro . Cell phenotype was analyzed by flow cytometry, colony formation was detected to study the proliferative ability. Osteogenic and adipogenic induction were performed. The osteogenic ability was explored by alizarin red staining, alkaline phosphatase (ALP) staining and ALP activity detection. Quantitative real-time polymerase chain reaction (qRT-PCR) was carried out to determine the mRNA expression levels of osteoblast marker genes. The adipogenic ability was detected by oil red O staining. Content of the bone was analyzed to observe the differences of bone imaging parameters including trabecular bone volume/tissue volume (BV/TV), bone surface area fraction/trabecular BV, trabecular number (Tb.N), and trabecular spacing (Tb.sp). Interleukin (IL)-1β was injected on WT mice of 2 months old and 18 months old, respectively. Difference in CKIP-1 expression was detected by RT-PCR and western blot. The relationship between CKIP-1 and inflammation was explored by RT-PCR and western blot. Results ALP assays, alizarin red staining, and qRT-PCR showed that MSCs derived from CKIP-1 KO mice exhibited a stronger capability for osteogenesis. Micro-computed tomography detection showed that among 18-month-old mice, CKIP-1 KO mice presented significantly higher bone mass compared with WT mice ( P = 0.02). No significant difference was observed in 2-month-old mice. In vivo data showed that expression of CKIP-1 was higher in the bone marrow of aging mice than in young mice (4.3-fold increase at the mRNA level, P = 0.04). Finally, the expression levels of CKIP-1 in bone marrow (3.2-fold increase at the mRNA level, P = 0.03) and cultured MSCs were up-regulated on chronic inflammatory stimulation by IL-1β. Conclusions CKIP-1 is responsible for negative regulation of MSC osteogenesis with age-dependent effects. Increasing levels of inflammation with aging may be the primary factor responsible for higher expression levels of CKIP-1 but may not necessarily affect MSC aging.

show abstract

“…At present, research on CKIP-1 mainly focuses on bone diseases. [14][15][16] Recently, the role of CKIP-1 in malignancies has attracted more attention. For example, studies have shown that CKIP-1 is a scaffold protein that may be involved in the tumorigenesis and progression of colorectal cancer, 5 non-Hodgkin's lymphoma 8 and glioma.…”

Section: Discussionmentioning

confidence: 99%

High expression of the CKIP-1 gene might promote apoptosis through downregulation of the Ras/ERK signalling pathway in the intestinal type of gastric cancer

Cao

et al. 2020

J Int Med Res

View full text Add to dashboard Cite

Objective: To investigate the effect of the casein kinase 2 interacting protein 1 (CKIP-1) on the apoptosis of the intestinal type of gastric cancer (GC). Methods: The levels of CKIP-1 protein and the rates of apoptosis were measured in tissue samples of the intestinal type of GC and human GC cell lines. The rate of apoptosis and the protein levels of B cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein (Bax), cleaved cysteinyl aspartate specific protease 3 (cleaved caspase-3), cleaved caspase-9, rat sarcoma (Ras), extracellular signal-regulated kinase 1 and 2 (ERK1/2) and phosphorylated extracellular signal-regulated kinase 1 and 2 (p-ERK1/2) were analysed in SGC7901 cells expressing CKIP-1 short hairpin RNA (shRNA; knockdown) and SGC7901 cells overexpressing CKIP-1. Results: The levels of CKIP-1 protein were significantly lower in the intestinal type of GC tissues compared with the samples of intestinal metaplasia. Both the levels of CKIP-1 protein and the levels of apoptosis decreased gradually with decreasing cell differentiation in the intestinal type of GC tissue and cell lines; and they were positively correlated. In the CKIP-1 shRNA group, the rate of apoptosis and the levels of Bax, cleaved caspase-3 and cleaved caspase-9 were decreased; and the levels of Bcl-2, Ras and the ratio of p-ERK/ERK were increased, compared with the control group. Opposite results were observed in the CKIP-1 overexpression group.

show abstract

The role of CKIP-1 in osteoporosis development and treatment

Cited by 31 publications

References 55 publications

A Synthetic Peptide, CK2.3, Inhibits RANKL-Induced Osteoclastogenesis through BMPRIa and ERK Signaling Pathway

A Synthetic Peptide, CK2.3, Inhibits RANKL-Induced Osteoclastogenesis through BMPRIa and ERK Signaling Pathway

Inflammation-mediated age-dependent effects of casein kinase 2-interacting protein-1 on osteogenesis in mesenchymal stem cells

High expression of the CKIP-1 gene might promote apoptosis through downregulation of the Ras/ERK signalling pathway in the intestinal type of gastric cancer

Contact Info

Product

Resources

About