Advertisement

Lycium barbarum polysaccharide protects against osteonecrosis of femoral head via regulating Runx2 expression

Published:January 11, 2022DOI:https://doi.org/10.1016/j.injury.2021.12.056

      Highlights

      • LBP enhanced osteoblast differentiation of BMSCs under hypoxia condition.
      • LBP treatment enhanced Runx2 and ALP expression in BMSCs.
      • LBP protects against ONFH via regulating Runx2 expression, which could be utilized to treat patients suffering ONFH.

      Abstract

      Background

      Osteonecrosis of femoral head (ONFH) is a pathological state caused by lack of blood supply in femoral head. This study aimed to explore the function of Lycium barbarum polysaccharide (LBP), an antioxidant agent extracted from L. barbarum, on ONFH.

      Methods

      Osteonecrosis rat model was generated using lipopolysaccharide (LPS) and methylprednisolone followed by examination of body weight, blood glucose, morphology, and BMSC osteoblast differentiation. The effect and underlying mechanism of LBP on the proliferation, apoptosis, and osteoblast differentiation of BMSC were determined with or without LPS or hypoxia treatment using CCK-8. Alizarin Red S staining, flow cytometry, and western blot, respectively.

      Result

      LBP could protect against glucocorticoid-induced ONFH in rats, resulting in improved sparse trabecular bone, empty lacunae and bone cell coagulation. Moreover, LBP promoted the proliferation and osteoblast differentiation of bone mesenchymal-derived stem cells (BMSCs) in a dose-dependent manner. Furthermore, LBP enhanced osteoblast differentiation of BMSCs under hypoxia condition. Mechanistically, we found that LBP treatment enhanced Runx2 and ALP expression in BMSCs. LBP restored the expression of Runx2 and ALP under hypoxia, suggesting that LBP might be involved in regulating Runx2/ALP expression and contributed to osteoblast differentiation. Knockdown of Runx2 significantly inhibited BMSCs proliferation, while LBP treatment did not rescue the osteoblast differentiation ability of BMSCs with Runx2 knockdown.

      Conclusion

      Our findings suggested that LBP protects against ONFH via regulating Runx2 expression, which could be utilized to treat patients suffering ONFH.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Injury
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Petek D.
        • Hannouche D.
        • Suva D.
        Osteonecrosis of the femoral head: pathophysiology and current concepts of treatment.
        EFORT Open Rev. 2019; 4: 85-97
        • Liu F.
        • Wang W.
        • Yang L.
        • Wang B.
        • Wang J.
        • Chai W.
        • et al.
        An epidemiological study of etiology and clinical characteristics in patients with nontraumatic osteonecrosis of the femoral head.
        J Res Med Sci. 2017; 22: 15
        • Tsai S.W.
        • Wu P.K.
        • Chen C.F.
        • Chiang C.C.
        • Huang C.K.
        • Chen T.H.
        • et al.
        Etiologies and outcome of osteonecrosis of the femoral head: etiology and outcome study in a Taiwan population.
        J Chin Med Assoc. 2016; 79: 39-45
        • Weinstein R.S.
        Glucocorticoid-induced osteonecrosis.
        Endocrine. 2012; 41: 183-190
        • Wang J.
        • Shi X.
        • Yang H.
        • Du J.
        • Ouyang Y.
        • Wang H.
        • et al.
        Association between alcohol-induced osteonecrosis of femoral head and risk variants of MMPS in Han population based on a case-control study.
        Oncotarget. 2017; 8: 64490-64498
        • Yombi J.C.
        • Vandercam B.
        • Wilmes D.
        • Dubuc J.E.
        • Vincent A.
        • Docquier P.L.
        Osteonecrosis of the femoral head in patients with type 1 human immunodeficiency virus infection: clinical analysis and review.
        Clin Rheumatol. 2009; 28: 815-823
        • Wang C.
        • Peng J.
        • Lu S.
        Summary of the various treatments for osteonecrosis of the femoral head by mechanism: a review.
        Exp Ther Med. 2014; 8: 700-706
        • Jilka R.L.
        • Noble B.
        • Weinstein R.S.
        Osteocyte apoptosis.
        Bone. 2013; 54: 264-271
        • Weinstein R.S.
        Clinical practice. Glucocorticoid-induced bone disease.
        N Engl J Med. 2011; 365: 62-70
        • Cao H.
        • Guan H.
        • Lai Y.
        • Qin L.
        • Wang X.
        Review of various treatment options and potential therapies for osteonecrosis of the femoral head.
        J Orthop Transl. 2016; 4: 57-70
        • Tang W.M.
        • Chan E.
        • Kwok C.Y.
        • Lee Y.K.
        • Wu J.H.
        • Wan C.W.
        • et al.
        A review of the anticancer and immunomodulatory effects of Lycium barbarum fruit.
        Inflammopharmacology. 2012; 20: 307-314
        • Liang B.
        • Peng L.
        • Li R.
        • Li H.
        • Mo Z.
        • Dai X.
        • et al.
        Lycium barbarum polysaccharide protects HSF cells against ultraviolet-induced damage through the activation of Nrf2.
        Cell Mol Biol Lett. 2018; 23: 18
        • Cao S.
        • Du J.
        • Hei Q.
        Lycium barbarum polysaccharide protects against neurotoxicity via the Nrf2-HO-1 pathway.
        Exp Ther Med. 2017; 14: 4919-4927
        • He Y.L.
        • Ying Y.
        • Xu Y.L.
        • Su J.F.
        • Luo H.
        • Wang H.F.
        [Effects of Lycium barbarum polysaccharide on tumor microenvironment T-lymphocyte subsets and dendritic cells in H22-bearing mice].
        Zhong Xi Yi Jie He Xue Bao. 2005; 3: 374-377
        • Zhou J.
        • Pang H.
        • Li W.
        • Liu Q.
        • Xu L.
        • Liu Q.
        • et al.
        Effects of Lycium barbarum polysaccharides on apoptosis, cellular adhesion, and oxidative damage in bone marrow mononuclear cells of mice exposed to ionizing radiation injury.
        Biomed Res Int. 2016; 20164147879
        • Zhu M.
        • Jinggang M.
        • ChangSheng H.
        • Haiping X.
        • Ning M.
        • Caijiao W.
        Extraction, characterization of polysaccharides from lycium barbarum and its effect on bone gene expression in rats.
        Carbohydr Polym. 2010; 80: 672-676
        • Zhang H.
        • Zheng L.
        • Yuan Z.
        Lycium barbarum polysaccharides promoted proliferation and differentiation in osteoblasts.
        J Cell Biochem. 2019; 120: 5018-5023
        • Yang L.
        • Boyd K.
        • Kaste S.C.
        • Kamdem Kamdem L.
        • Rahija R.J.
        • Relling M.V
        A mouse model for glucocorticoid-induced osteonecrosis: effect of a steroid holiday.
        J Orthop Res. 2009; 27: 169-175
        • Bi H.
        • Ming L.
        • Cheng R.
        • Luo H.
        • Zhang Y.
        • Jin Y.
        Liver extracellular matrix promotes BM-MSCs hepatic differentiation and reversal of liver fibrosis through activation of integrin pathway.
        J Tissue Eng Regen Med. 2017; 11: 2685-2698
        • Nozaki Y.
        • Kumagai K.
        • Miyata N.
        • Niwa M.
        Pravastatin reduces steroid-induced osteonecrosis of the femoral head in SHRSP rats.
        Acta Orthop. 2012; 83: 87-92
        • Mikami T.
        • Ichiseki T.
        • Kaneuji A.
        • Ueda Y.
        • Sugimori T.
        • Fukui K.
        • et al.
        Prevention of steroid-induced osteonecrosis by intravenous administration of vitamin E in a rabbit model.
        J Orthop Sci. 2010; 15: 674-677
        • Deng S.
        • Zhou J.L.
        • Fang H.S.
        • Nie Z.G.
        • Chen S.
        • Peng H
        Sesamin protects the femoral head from osteonecrosis by inhibiting ROS-induced osteoblast apoptosis in rat model.
        Front Physiol. 2018; 9: 1787
        • Lou L.
        • Chen G.
        • Zhong B.
        • Liu F.
        Lycium barbarum polysaccharide induced apoptosis and inhibited proliferation in infantile hemangioma endothelial cells via down-regulation of PI3K/AKT signaling pathway.
        Biosci Rep. 2019; : 39
        • Wang H.
        • Lau B.W.
        • Wang N.L.
        • Wang S.Y.
        • Lu Q.J.
        • Chang R.C.
        • et al.
        Lycium barbarum polysaccharides promotes in vivo proliferation of adult rat retinal progenitor cells.
        Neural Regen Res. 2015; 10: 1976-1981
        • Ming W.
        • Liquan G.
        Anti-fatigue and anti-hypoxic effects of Lycium barbarum polysaccharides.
        International Conference on Advances in Energy, Environment and Chemical Engineering. 2015; : 686-689
        • Du M.
        • Hu X.
        • Kou L.
        • Zhang B.
        • Zhang C.
        Lycium barbarum polysaccharide mediated the antidiabetic and antinephritic effects in diet-streptozotocin-induced diabetic Sprague Dawley rats via regulation of NF-κB.
        BioMed Res Int. 2016; (2016)
        • Li X.M.
        • Ma Y.L.
        • Liu X.J.
        Effect of the Lycium barbarum polysaccharides on age-related oxidative stress in aged mice.
        J Ethnopharmacol. 2007; 111: 504-511
        • Wang J.
        • Tian L.
        • He L.
        • Chen N.
        • Ramakrishna S.
        • So K.F.
        • et al.
        Lycium barbarum polysaccharide encapsulated poly lactic-co-glycolic acid nanofibers: cost effective herbal medicine for potential application in peripheral nerve tissue engineering.
        Sci Rep. 2018; 8: 8669
        • Hong C.Y.
        • Zhang H.D.
        • Liu X.Y.
        • Xu Y.
        Attenuation of hyperoxic acute lung injury by Lycium barbarum polysaccharide via inhibiting NLRP3 inflammasome.
        Arch Pharm Res. 2019; 42: 902-908
        • Wang W.
        • Xin J.
        • Chen W.
        • Jing L.
        • Zhang P.
        Icariin alleviates hypoxia-induced damage in MC3T3-E1 cells by downregulating TALNEC2.
        Biotechnol Appl Biochem. 2020; 67: 1000-1010
        • Ma X.L.
        • Liu Z.P.
        • Ma J.X.
        • Han C.
        • Zang J.C.
        Dynamic expression of Runx2, Osterix and AJ18 in the femoral head of steroid-induced osteonecrosis in rats.
        Orthop Surg. 2010; 2: 278-284
        • Fujita T.
        • Azuma Y.
        • Fukuyama R.
        • Hattori Y.
        • Yoshida C.
        • Koida M.
        • et al.
        Runx2 induces osteoblast and chondrocyte differentiation and enhances their migration by coupling with PI3K-Akt signaling.
        J Cell Biol. 2004; 166: 85-95
        • Kawahata H.
        • Kikkawa T.
        • Higashibata Y.
        • Sakuma T.
        • Huening M.
        • Sato M.
        • et al.
        Enhanced expression of Runx2/PEBP2alphaA/CBFA1/AML3 during fracture healing.
        J Orthop Sci. 2003; 8: 102-108
        • Kong L.
        • Zuo R.
        • Wang M.
        • Wang W.
        • Xu J.
        • Chai Y.
        • et al.
        Silencing MicroRNA-137-3p, which targets Runx2 and CXCL12 prevents steroid-induced osteonecrosis of the femoral head by facilitating osteogenesis and angiogenesis.
        Int J Biol Sci. 2020; 16: 655-670
        • Chen X.
        • Li J.
        • Liang D.
        • Zhang L.
        • Wang Q.
        LncRNA AWPPH participates in the development of non-traumatic osteonecrosis of femoral head by upregulating Runx2.
        Exp Ther Med. 2020; 19: 153-159
        • Zhang H.
        • Zheng L.
        • Yuan Z.
        Lycium barbarum polysaccharides promoted proliferation and differentiation in osteoblasts.
        J Cell Biochem. 2019; 120: 5018-5023
        • Jun J.H.
        • Yoon W.J.
        • Seo S.B.
        • Woo K.M.
        • Kim G.S.
        • Ryoo H.-.M.
        • et al.
        BMP2-activated Erk/MAP kinase stabilizes Runx2 by increasing p300 levels and histone acetyltransferase activity.
        J Biol Chem. 2010; 285: 36410-36419