title: Role of dentin matrix protein 1 in cartilage redifferentiation and osteoarthritis.
abstract: OBJECTIVE
  The aim of this study was to test the possible involvement, relevance and significance of dentin matrix protein 1 (DMP1) in chondrocyte redifferentiation and OA.
  
  
  METHODS
  To examine the function of DMP1 in vitro, bone marrow stromal cells (BMSCs) and articular chondrocytes (ACs) were isolated and differentiated in micromasses in the presence or absence of DMP1 small interfering RNA and analysed for chondrogenic phenotype. The association of DMP1 expression with OA progression was analysed time dependently in the OA menisectomy rat model and in grade-specific OA human samples.
  
  
  RESULTS
  It was found that DMP1 was strongly related to chondrogenesis, which was evidenced by the strong expression of DMP1 in the 14.5-day mouse embryonic cartilage development stage and in femoral heads of post-natal days 0 and 4. In vitro chondrogenesis in BMSCs and ACs was accompanied by a gradual increase in DMP1 expression at both the gene and protein levels. In addition, knockdown of DMP1 expression led to decreased chondrocyte marker genes, such as COL2A1, ACAN and SOX9, and an increase in the expression of COL10A and MMP13 in ACs. Moreover, treatment with IL-1β, a well-known catabolic culprit of proteoglycan matrix loss, significantly reduced the expression of DMP1. Furthermore, we also observed the suppression of DMP1 protein in a grade-specific manner in knee joint samples from patients with OA. In the menisectomy-induced OA model, an increase in the Mankin score was accompanied by the gradual loss of DMP1 expression.
  
  
  CONCLUSIONS
  Observations from this study suggest that DMP1 may play an important role in maintaining the chondrogenic phenotype and its possible involvement in altered cartilage matrix remodelling and degradation in disease conditions like OA.
authors.affiliation: Medical Device Domain, Institute of Health and Biomedical Innovation, Queensland University of Technology and Orthopaedic Department, Prince Charles Hospital, Brisbane, Queensland, Brisbane, Australia. i.prasadam@qut.edu.au.
authors.forename: Indira
authors.initials: I
authors.lastname: Prasadam
authors.affiliation: Medical Device Domain, Institute of Health and Biomedical Innovation, Queensland University of Technology and Orthopaedic Department, Prince Charles Hospital, Brisbane, Queensland, Brisbane, Australia.
authors.forename: Yinghong
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Medical Device Domain, Institute of Health and Biomedical Innovation, Queensland University of Technology and Orthopaedic Department, Prince Charles Hospital, Brisbane, Queensland, Brisbane, Australia.
authors.forename: Wei
authors.initials: W
authors.lastname: Shi
authors.affiliation: Medical Device Domain, Institute of Health and Biomedical Innovation, Queensland University of Technology and Orthopaedic Department, Prince Charles Hospital, Brisbane, Queensland, Brisbane, Australia. Medical Device Domain, Institute of Health and Biomedical Innovation, Queensland University of Technology and Orthopaedic Department, Prince Charles Hospital, Brisbane, Queensland, Brisbane, Australia.
authors.forename: Ross
authors.initials: R
authors.lastname: Crawford
authors.affiliation: Medical Device Domain, Institute of Health and Biomedical Innovation, Queensland University of Technology and Orthopaedic Department, Prince Charles Hospital, Brisbane, Queensland, Brisbane, Australia.
authors.forename: Yin
authors.initials: Y
authors.lastname: Xiao
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000378:metabolism; D002358:Cartilage, Articular / Q000196:embryology / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism* / Q000473:pathology; D020219:Chondrogenesis / Q000502:physiology; D018450:Disease Progression; D047108:Embryonic Development / Q000502:physiology; D016326:Extracellular Matrix Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology; D008297:Male; D051379:Mice; D020370:Osteoarthritis, Knee / Q000378:metabolism* / Q000473:pathology; D010750:Phosphoproteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D011921:Rats, Inbred WKY
chemical_list: C513309:DMP1 protein, human; C081635:Dmp1 protein, rat; D016326:Extracellular Matrix Proteins; D053583:Interleukin-1beta; D010750:Phosphoproteins; D034741:RNA, Small Interfering
keywords: cartilage; chondrocytes; dentin matrix protein 1; osteoarthritis; redifferentiation