Skip to main content
Log in

Crocin promotes osteogenesis differentiation of bone marrow mesenchymal stem cells

  • Published:
In Vitro Cellular & Developmental Biology - Animal Aims and scope Submit manuscript

Abstract

Crocin has plentiful pharmacological effects, but its role in osteogenesis differentiation of bone marrow mesenchymal stem cells (BMSCs) is unexplored. This study explored the effect of crocin on osteogenesis differentiation, in order to provide evidence for its clinical application. In cell experiments, human BMSCs (hBMSCs) were induced by osteogenesis differentiation medium or crocin. In animal experiments, steroid-induced osteonecrosis of the femoral head (SANFH) rat models was established using lipopolysaccharide (LPS) plus methylprednisolone (MPS), and then treated with crocin. The osteogenesis differentiation capacity of hBMSCs was analyzed by alkaline phosphatase (ALP) and alizarin red S staining. Histopathological changes in rat femoral head tissues were observed by hematoxylin and eosin (H&E) staining. The expression levels of RUNX2, COL1A1, OCN, and GSK-3β in hBMSCs and rat femoral head tissues were measured by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot (WB) analysis. ALP and alizarin red S staining demonstrated that LAP activity and calcium nodules were increased in hBMSCs treated with crocin. From H&E staining results, femoral head tissues of SANFH models showed typical osteonecrosis, which could be ameliorated by crocin. WB and qRT-PCR assays detected that the expression levels of RUNX2, COL1A1, and OCN in hBMSCs and femoral head tissues of models were obviously increased after crocin treatment, while GSK-3β phosphorylation was reduced. In general, the action of crocin was concentration-dependent. Crocin might be beneficial to the recovery of SANFH through accelerating osteogenesis differentiation of BMSCs, which might be a novel therapy for related diseases.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Figure 1.
Figure 2.
Figure 3.
Figure 4.

Similar content being viewed by others

References

  • Arai R, Takahashi D, Inoue M, Irie T, Iwasaki N (2017) Efficacy of teriparatide in the treatment of nontraumatic osteonecrosis of the femoral head: a retrospective comparative study with alendronate Bmc Musculoskeletal Disorders 18

  • Arioka M et al. (2013) Acceleration of bone development and regeneration through the Wnt/beta-catenin signaling pathway in mice heterozygously deficient for GSK-3beta biochemical and biophysical research communications 440:677-682 https://doi.org/10.1016/j.bbrc.2013.09.126

  • Bardai G et al. (2016) Osteogenesis imperfecta type I caused by COL1A1 deletions calcified tissue international 98:76-84 https://doi.org/10.1007/s00223-015-0066-6

  • Cai T, Sun D, Duan Y, Wen P, Dai C, Yang J, He W (2016) WNT/beta-catenin signaling promotes VSMCs to osteogenic transdifferentiation and calcification through directly modulating Runx2 gene expression. Exp Cell Res 345:206–217. https://doi.org/10.1016/j.yexcr.2016.06.007

    Article  CAS  PubMed  Google Scholar 

  • Chava S, Chennakesavulu S, Gayatri BM, Reddy ABM (2018) A novel phosphorylation by AMP-activated kinase regulates RUNX2 from ubiquitination in osteogenesis over adipogenesis cell death & disease 9:754 https://doi.org/10.1038/s41419-018-0791-7

  • Ching HS, Luddin N, Rahman IA, Ponnuraj KT (2017) Expression of odontogenic and osteogenic markers in DPSCs and SHED: a review current stem cell research & therapy 12:71–79 https://doi.org/10.2174/1574888x11666160815095733

  • Christodoulou E, Kadoglou NP, Kostomitsopoulos N, Valsami G (2015) Saffron: a natural product with potential pharmaceutical applications. J Pharm Pharmacol 67:1634–1649. https://doi.org/10.1111/jphp.12456

    Article  CAS  PubMed  Google Scholar 

  • Dai F, Du P, Chang Y, Ji E, Xu Y, Wei C, Li J (2018) Downregulation of MiR-199b-5p inducing differentiation of bone-marrow mesenchymal stem cells (BMSCs) toward cardiomyocyte-like cells via HSF1/HSP70 pathway medical science monitor : international medical journal of experimental and clinical research 24:2700-2710 https://doi.org/10.12659/msm.907441

  • Faienza MF et al. (2014) Treatment of osteoporosis in children with glucocorticoid-treated diseases expert review of endocrinology & metabolism 9:525-534 https://doi.org/10.1586/17446651.2014.936384

  • García-Olmo DC, Riese HH, Escribano J, Ontañón J, Fernandez JA, Atiénzar M, García-Olmo D (1999) Effects of long-term treatment of colon adenocarcinoma with crocin, a carotenoid from saffron (Crocus sativus L.): an experimental study in the rat. Nutr Cancer 35:120–126. https://doi.org/10.1207/s15327914nc352_4

    Article  PubMed  Google Scholar 

  • Gu M, Luo L, Fang K (2018) Crocin inhibits obesity via AMPK-dependent inhibition of adipocyte differentiation and promotion of lipolysis. Biosci Trends 12:587–594. https://doi.org/10.5582/bst.2018.01240

    Article  CAS  PubMed  Google Scholar 

  • Hao C et al (2016) MiR-708 promotes steroid-induced osteonecrosis of femoral head, suppresses osteogenic differentiation by targeting SMAD3. Sci Rep 6:22599. https://doi.org/10.1038/srep22599

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • He Y, Zhou L, Fan Z, Liu S, Fang W (2018) Palmitic acid, but not high-glucose, induced myocardial apoptosis is alleviated by Nacetylcysteine due to attenuated mitochondrial-derived ROS accumulation-induced endoplasmic reticulum stress. Cell Death Dis 9:568. https://doi.org/10.1038/s41419-018-0593-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huang L, Wang Y, Jiang Y, Wu Y, Hu C, Ouyang H (2018) High levels of GSK-3beta signalling reduce osteogenic differentiation of stem cells in osteonecrosis of femoral head. J Biochem 163:243–251. https://doi.org/10.1093/jb/mvx076

    Article  CAS  PubMed  Google Scholar 

  • Kalalinia F, Ghasim H, Amel Farzad S, Pishavar E, Ramezani M, Hashemi M (2018) Comparison of the effect of crocin and crocetin, two major compounds extracted from saffron, on osteogenic differentiation of mesenchymal stem cells. Life Sci 208:262–267. https://doi.org/10.1016/j.lfs.2018.07.043

    Article  CAS  PubMed  Google Scholar 

  • Kubo T, Ueshima K, Saito M, Ishida M, Arai Y, Fujiwara H (2016) Clinical and basic research on steroid-induced osteonecrosis of the femoral head in Japan Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association 21:407–413 https://doi.org/10.1016/j.jos.2016.03.008

  • Lei M, Guo C, Hua L, Xue S, Yu D, Zhang C, Wang D (2017) Crocin attenuates joint pain and muscle dysfunction in osteoarthritis rat inflammation 40:2086–2093 https://doi.org/10.1007/s10753-017-0648-8

  • Lei Q, Lin D, Huang WX, Wu D, Chen J (2018) [Effects of calcium ion on the migration and osteogenic differentiation of human osteoblasts] Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology 36:602-608 https://doi.org/10.7518/hxkq.2018.06.004

  • Li C, Wei GJ, Xu L, Rong JS, Tao SQ, Wang YS (2017) The involvement of senescence induced by the telomere shortness in the decline of osteogenic differentiation in BMSCs European review for medical and pharmacological sciences 21:1117–1124

  • Liu FF, Zhao S, Liu P, Huo SP (2018) Influence of mTOR signaling pathway on ketamine-induced injuries in the hippocampal neurons of rats Neurol Res:1-10 https://doi.org/10.1080/01616412.2018.1531203

  • Moshiri M, Vahabzadeh M, Hosseinzadeh H (2015) Clinical applications of saffron (Crocus sativus) and its constituents: a review. Drug Research 65:287–295. https://doi.org/10.1055/s-0034-1375681

    Article  CAS  PubMed  Google Scholar 

  • Nie B, Ao H, Zhou J, Tang T, Yue B (2016) Biofunctionalization of titanium with bacitracin immobilization shows potential for anti-bacteria, osteogenesis and reduction of macrophage inflammation. Colloids Surf B: Biointerfaces 145:728–739. https://doi.org/10.1016/j.colsurfb.2016.05.089

    Article  CAS  PubMed  Google Scholar 

  • Pei J, Fan L, Nan K, Li J, Shi Z, Dang X, Wang K (2017) Excessive activation of TLR4/NF-kappaB interactively suppresses the canonical Wnt/beta-catenin pathway and induces SANFH in SD. Rats Scientific Reports 7:11928. https://doi.org/10.1038/s41598-017-12196-8

    Article  CAS  PubMed  Google Scholar 

  • Qin L et al (2006) Multiple bioimaging modalities in evaluation of an experimental osteonecrosis induced by a combination of lipopolysaccharide and methylprednisolone. Bone 39:863–871. https://doi.org/10.1016/j.bone.2006.04.018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rahman WA, Garbuz DS, Masri BA (2013) Total hip arthroplasty in steroid-induced osteonecrosis: early functional and radiological outcomes. Can J Surg J canadien de chirurgie 56:41–46. https://doi.org/10.1503/cjs.032510

    Article  Google Scholar 

  • Rao X, Huang X, Zhou Z, Lin X (2013) An improvement of the 2^(-delta delta CT) method for quantitative real-time polymerase chain reaction data analysis Biostatistics, bioinformatics and biomathematics 3:71-85

  • Rauch A et al (2019) Osteogenesis depends on commissioning of a network of stem cell transcription factors that act as repressors of adipogenesis. Nat Genet 51:716–727. https://doi.org/10.1038/s41588-019-0359-1

    Article  CAS  PubMed  Google Scholar 

  • Siller AF, Whyte MP (2018) Alkaline phosphatase: discovery and naming of our favorite enzyme. J Bone Miner Res 33:362–364. https://doi.org/10.1002/jbmr.3225

    Article  PubMed  Google Scholar 

  • Suh KS, Chon S, Jung WW, Choi EM (2019) Crocin attenuates methylglyoxal-induced osteoclast dysfunction by regulating glyoxalase, oxidative stress, and mitochondrial function Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 124:367-373 https://doi.org/10.1016/j.fct.2018.12.031

  • Sun ZB et al. (2015) Icariin may benefit the mesenchymal stem cells of patients with steroid-associated osteonecrosis by ABCB1-promoter demethylation: a preliminary study Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA 26:187-197 https://doi.org/10.1007/s00198-014-2809-z

  • Tang SL, Huang QH, Wu LG, Liu C, Cai AL (2018) MiR-124 regulates osteoblast differentiation through GSK-3β in ankylosing spondylitis European review for medical and pharmacological sciences 22:6616–6624 https://doi.org/10.26355/eurrev_201810_16136

  • Wang A, Ren M, Wang J (2018a) The pathogenesis of steroid-induced osteonecrosis of the femoral head: a systematic review of the literature. Gene 671:103–109. https://doi.org/10.1016/j.gene.2018.05.091

    Article  CAS  PubMed  Google Scholar 

  • Wang P et al. (2016) Effect of Colla Cornus Cervi combined with LV-mediated BMP7 transfected BMSCS on ANFH in rats Acta poloniae pharmaceutica 73:1521-1530

  • Wang Q, Yang Q., Chen G., du Z., Ren M., Wang A., Zhao H., Li Z., Zhang G., Song Y. (2018b) LncRNA expression profiling of BMSCs in osteonecrosis of the femoral head associated with increased adipogenic and decreased osteogenic differentiation Scientific reports 8:9127 https://doi.org/10.1038/s41598-018-27501-2

  • Wang XS, Zhuang QY, Weng XS, Lin J, Jin J, Qian WW (2013) Etiological and clinical analysis of osteonecrosis of the femoral head in Chinese patients. Chin Med J 126:290–295

    PubMed  Google Scholar 

  • Zhang K et al. (2019) The PERK-EIF2alpha-ATF4 signaling branch regulates osteoblast differentiation and proliferation by PTH American journal of physiology endocrinology and metabolism 316:E590-e604 https://doi.org/10.1152/ajpendo.00371.2018

  • Zhao R, Li Y, Lin Z, Wan J, Xu C, Zeng Y, Zhu Y (2016) miR-199b-5p modulates BMSC osteogenesis via suppressing GSK-3beta/beta-catenin signaling pathway Biochemical and biophysical research communications 477:749-754 https://doi.org/10.1016/j.bbrc.2016.06.130

Download references

Funding

This manuscript was supported by the funding of Health industry research project (No. 201402016).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Dewei Zhao.

Additional information

Editor: Tetsuji Okamoto

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, B., Qin, K., Wang, B. et al. Crocin promotes osteogenesis differentiation of bone marrow mesenchymal stem cells. In Vitro Cell.Dev.Biol.-Animal 56, 680–688 (2020). https://doi.org/10.1007/s11626-020-00487-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11626-020-00487-w

Keywords

Navigation