title: Kaempferol slows intervertebral disc degeneration by modifying LPS-induced osteogenesis/adipogenesis imbalance and inflammation response in BMSCs.
abstract: Intervertebral disc (IVD) degeneration is a common disease that represents a significant cause of socio-economic problems. Bone marrow-derived mesenchymal stem cells (BMSCs) are a potential autologous stem cell source for the nucleus pulposus regeneration. Kaempferol has been reported to exert protective effects against both osteoporosis and obesity. This study explored the effect of kaempferol on BMSCs differentiation and inflammation. The results demonstrated that kaempferol did not show any cytotoxicity at concentrations of 20, 60 and 100μM. Kaempferol enhanced cell viability by counteracting the lipopolysaccharide (LPS)-induced cell apoptosis and increasing cell proliferation. Western blot analysis of mitosis-associated nuclear antigen (Ki67) and proliferation cell nuclear antigen (PCNA) further confirmed the increased effect of kaempferol on LPS-induced decreased viability of BMSCs. Besides, kaempferol elevated LPS-induced reduced level of chondrogenic markers (SOX-9, Collagen II and Aggrecan), decreased the level of matrix-degrading enzymes, i.e., matrix metalloprotease (MMP)-3 and MMP-13, suggesting the osteogenesis of BMSC under kaempferol treatment. On the other hand, kaempferol enhanced LPS-induced decreased expression of lipid catabolism-related genes, i.e., carnitine palmitoyl transferase-1 (CPT-1). Kaempferol also suppressed the expression of lipid anabolism-related genes, i.e., peroxisome proliferators-activated receptor-γ (PPAR-γ). The Oil red O staining further convinced the inhibition effect of kaempferol on BMSCs adipogenesis. In addition, kaempferol alleviated inflammatory by reducing the level of pro-inflammatory cytokines (i.e., interleukin (IL)-6) and increasing anti-inflammatory cytokine (IL-10) via inhibiting the nucleus translocation of nuclear transcription factor (NF)-κB p65. Taken together, our research indicated that kaempferol may serve as a novel target for treatment of IVD degeneration.
authors.affiliation: Minimally invasive Department of Orthopedics, The first people's Hospital of Huaihua, 418000, Hunan, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Minimally invasive Department of Orthopedics, The first people's Hospital of Huaihua, 418000, Hunan, PR China.
authors.forename: Haoyu
authors.initials: H
authors.lastname: Tang
authors.affiliation: Minimally invasive Department of Orthopedics, The first people's Hospital of Huaihua, 418000, Hunan, PR China.
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Minimally invasive Department of Orthopedics, The first people's Hospital of Huaihua, 418000, Hunan, PR China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Minimally invasive Department of Orthopedics, The first people's Hospital of Huaihua, 418000, Hunan, PR China.
authors.forename: Chengfeng
authors.initials: C
authors.lastname: Qiu
authors.affiliation: Minimally invasive Department of Orthopedics, The first people's Hospital of Huaihua, 418000, Hunan, PR China.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Minimally invasive Department of Orthopedics, The first people's Hospital of Huaihua, 418000, Hunan, PR China.
authors.forename: Pinge
authors.initials: P
authors.lastname: Huang
authors.affiliation: Minimally invasive Department of Orthopedics, The first people's Hospital of Huaihua, 418000, Hunan, PR China. Electronic address: orthop_lifeng@163.com.
authors.forename: Feng
authors.initials: F
authors.lastname: Li
mesh_terms: D050156:Adipogenesis / Q000187:drug effects; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000502:physiology; D002334:Carnitine O-Palmitoyltransferase / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000188:drug therapy*; D018836:Inflammation Mediators / Q000378:metabolism; D055959:Intervertebral Disc Degeneration / Q000188:drug therapy*; D044949:Kaempferols / Q000627:therapeutic use*; D008070:Lipopolysaccharides / Q000276:immunology; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000502:physiology; D010012:Osteogenesis / Q000187:drug effects; D047495:PPAR gamma / Q000378:metabolism; D011817:Rabbits; D055758:SOX9 Transcription Factor / Q000235:genetics / Q000378:metabolism
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D044949:Kaempferols; D008070:Lipopolysaccharides; D047495:PPAR gamma; D055758:SOX9 Transcription Factor; C006552:kaempferol; D002334:Carnitine O-Palmitoyltransferase; D019278:Matrix Metalloproteinase 3
keywords: Adipogenesis; BMSCs; IVD degeneration; Inflammation; Kaempferol; Osteogenesis