Cystatin C stimulates the differentiation of mouse osteoblastic cells and bone formation

Danjo, Atsushi; Yamaza, Takayoshi; Kido, Mizuho A.; Shimohira, Daiji; Tsukuba, Takayuki; Kagiya, Tadayoshi; Yamashita, Yoshio; Nishijima, Kiyoto; Masuko, Sadahiko; Goto, Masaaki; Takano, Teruo

doi:10.1016/j.bbrc.2007.06.028

Cited by 40 publications

(48 citation statements)

References 25 publications

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“…These results are in agreement with those studies which highlight that PO and BPH patients present increased levels of IL-6 and that this phenomenon appears to be correlated with the specific involvement of this pleiotropic cytokine in the pathogenesis of these inflammatory diseases [1,19,25,26]. On the other hand, the altered levels of cystatin C observed in PO patients further support the hypothesis that this inhibitor appears to play an active role in bone remodeling processes [8,[27][28][29]. However, these observations and the results obtained by the ROC curve analysis seem to rule out that, at least in breast cancer, IL-6 and Cyst C may be of clinical usefulness as specific markers of metastatic bone disease.…”

Section: Discussionsupporting

confidence: 94%

“…These data further confirm and extent previous observations from other studies which show that the infusion of ZA to patients with metastatic breast cancer induces a not statistically significant increase of the circulating levels of IL-6 up to 7 days after drug administration [30]. On the other hand, as IL-6 and Cyst C have been shown to stimulate osteoblast production and differentiation and to inhibit osteoclastogenesis [2,3,8,[27][28][29] it is conceivable to speculate that the increased levels of these molecules induced by ZA in PCa patients with bone metastases may likely reflect an enhanced osteoblastic activity, which in PCa is predominant [31,32], elicited by the drug. This hypothesis is further corroborated by some in vitro studies which highlight that ZA stimulate the proliferation and differentiation of normal human osteoblasts [33].…”

Section: Discussionsupporting

confidence: 91%

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Serum interleukin-6 in patients with metastatic bone disease: correlation with cystatin C

et al. 2008

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The clinical significance of serum interleukin-6 (IL-6) and its correlation with cystatin C (Cyst C), an endogenous inhibitor of cysteine proteinase cathepsin K, was investigated by immunoassays in patients with bone metastasis from breast cancer (BCa) or prostate cancer (PCa). Additional studies were also performed in these patients to assess the effects of zoledronic acid (ZA) administration on the circulating levels of these molecules. Mean IL-6 and Cyst C serum concentrations were significantly increased in BCa patients and in patients with primary osteoporosis (PO) compared to healthy subjects (HS). However, Cyst C, but not IL-6, resulted significantly more elevated in BCa patients than in PO patients. Furthermore, in BCa patients no correlation was highlighted between IL-6 and Cyst C or between these molecules and some clinicobiological parameters of malignant progression. Mean IL-6 levels were also higher in PCa patients and in patients with benign prostatic hyperplasia (BPH) than in HS while Cyst C resulted significantly higher in PCa but not in BPH patients as compared to HS. In PCa patients, a positive correlation was highlighted between IL-6 and number of bone metastases or serum prostate-specific antigen but not with the Gleason score. Conversely, Cyst C levels did not correlate with any of the parameters considered above or with IL-6. Receiver operating characteristic (ROC) curve analysis showed a poor diagnostic accuracy of IL-6 and Cyst C to detect BCa patients with skeletal metastases while, in PCa patients, only IL-6 showed a fair diagnostic performance in this respect. Finally, the administration of ZA to patients with bone metastases induced a statistically significant increase of serum IL-6 and Cyst C only PCa patients with bone metastasis. These data indicate that IL-6 and Cyst C may be regarded as novel targets for cancer treatment and as markers of increased osteoblastic activity associated to bisphosphonate treatments in PCa patients with bone metastases.

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Section: Discussionsupporting

confidence: 94%

Section: Discussionsupporting

confidence: 91%

Serum interleukin-6 in patients with metastatic bone disease: correlation with cystatin C

et al. 2008

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“…Lactoperoxidase was originally identified as an inhibitory factor of mouse osteoclastogenesis. Cystatin C also appeared to stimulate the differentiation of mouse osteoblastic cells and bone formation (Danjo et al, 2007). Taken together, these findings suggest that components of MBP other than LF may influence bone metabolism, by regulating bone formation and bone resorption.…”

Section: Discussionmentioning

confidence: 93%

The bone-strengthening activity of milk basic protein is not dependent on lactoferrin

Morita

Ono-Ohmachi

Higurashi

et al. 2012

International Dairy Journal

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“…The downregulated expression of several genes in pMSCs after co-culture (e. g. CST3 [76], FZD5 [72], WNT3 [77], C/EBPB [78], and GLI1 [79]; see Supp. Table S3) may also contribute to the reported impairment of OB function in MM.…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic profile induced in bone marrow mesenchymal stromal cells after interaction with multiple myeloma cells: implications in myeloma progression and myeloma bone disease

et al. 2014

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Despite evidence about the implication of the bone marrow (BM) stromal microenvironment in multiple myeloma (MM) cell growth and survival, little is known about the effects of myelomatous cells on BM stromal cells. Mesenchymal stromal cells (MSCs) from healthy donors (dMSCs) or myeloma patients (pMSCs) were co-cultured with the myeloma cell line MM.1S, and the transcriptomic profile of MSCs induced by this interaction was analyzed. Deregulated genes after co-culture common to both d/pMSCs revealed functional involvement in tumor microenvironment cross-talk, myeloma growth induction and drug resistance, angiogenesis and signals for osteoclast activation and osteoblast inhibition. Additional genes induced by co-culture were exclusively deregulated in pMSCs and predominantly associated to RNA processing, the ubiquitine-proteasome pathway, cell cycle regulation, cellular stress and non-canonical Wnt signaling. The upregulated expression of five genes after co-culture (CXCL1, CXCL5 and CXCL6 in d/pMSCs, and Neuregulin 3 and Norrie disease protein exclusively in pMSCs) was confirmed, and functional in vitro assays revealed putative roles in MM pathophysiology. The transcriptomic profile of pMSCs co-cultured with myeloma cells may better reflect that of MSCs in the BM of myeloma patients, and provides new molecular insights to the contribution of these cells to MM pathophysiology and to myeloma bone disease.

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Cystatin C stimulates the differentiation of mouse osteoblastic cells and bone formation

Cited by 40 publications

References 25 publications

Serum interleukin-6 in patients with metastatic bone disease: correlation with cystatin C

Serum interleukin-6 in patients with metastatic bone disease: correlation with cystatin C

The bone-strengthening activity of milk basic protein is not dependent on lactoferrin

Transcriptomic profile induced in bone marrow mesenchymal stromal cells after interaction with multiple myeloma cells: implications in myeloma progression and myeloma bone disease

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