본문 바로가기
KERD
논문KCI 등재후보

관절연골 재생을 위한 골수유래 중간엽 줄기세포의 특이적 케모카인

Mesenchymal Stem Cell-Specific Chemokines for Articular Cartilage Repair

0

조회

0

다운로드

0

인용

0

참고문헌

키워드

주제분류기타의약학

초록

Objectives: Bone marrow-derived mesenchymal stem cells (BMSCs) are a good source for cartilage repair. Chondral defects do not heal spontaneously due to a lack of chondrocytes at the defect site and migration of surrounding chondrocytes to the injury site. The purpose of this study was to determine the expression of 19 chemokine receptors in human BMSCs stimulated by IL-1β and TNF-α as an in vitro cartilage-injury condition. Materials & Methods: MSCs isolated from human bone marrow were expended for the experiments. Specifically, cells were grown either in the presence or absence of pro-inflammatory cytokines, such as IL-1β and TNF-α. RT-PCR was performed to evaluate the expression of 19 chemokine receptors. To evaluate changes in the expression of chemokine receptors, a reverse dot-blot assay was performed. Results: We observed increased expression of CCR4, CCR6, CCR7, CCR9, CCR10, CXCR1, CXCR4, CXCR6, and CXCR7 in untreated BMSCs, while inflammation-induced BMSCs exhibited enhanced expression of CCR9, CCR10, CXCR1, CXCR4, CXCR5, CXCR6, and CXCR7. Collectively, the results showed CCR9/ CYA-25, CCR10/SCYA-28, CXCR1/IL-8, CXCR4/SDF-1, CXCR6/CXCL-16, and CXCR7/SDF-1 (receptor/ligand) were expressed in normal BMSCs and showed a gradual increase upon treatment with pro-inflammatory cytokines. Conclusions: We suggest that chemokines, including SCYA-25, SCYA-28, IL-8, CXCL-16 and SDF-1 can be useful in repairing damaged articular cartilage.

Abstract

Objectives: Bone marrow-derived mesenchymal stem cells (BMSCs) are a good source for cartilage repair. Chondral defects do not heal spontaneously due to a lack of chondrocytes at the defect site and migration of surrounding chondrocytes to the injury site. The purpose of this study was to determine the expression of 19 chemokine receptors in human BMSCs stimulated by IL-1β and TNF-α as an in vitro cartilage-injury condition. Materials & Methods: MSCs isolated from human bone marrow were expended for the experiments. Specifically, cells were grown either in the presence or absence of pro-inflammatory cytokines, such as IL-1β and TNF-α. RT-PCR was performed to evaluate the expression of 19 chemokine receptors. To evaluate changes in the expression of chemokine receptors, a reverse dot-blot assay was performed. Results: We observed increased expression of CCR4, CCR6, CCR7, CCR9, CCR10, CXCR1, CXCR4, CXCR6, and CXCR7 in untreated BMSCs, while inflammation-induced BMSCs exhibited enhanced expression of CCR9, CCR10, CXCR1, CXCR4, CXCR5, CXCR6, and CXCR7. Collectively, the results showed CCR9/ CYA-25, CCR10/SCYA-28, CXCR1/IL-8, CXCR4/SDF-1, CXCR6/CXCL-16, and CXCR7/SDF-1 (receptor/ligand) were expressed in normal BMSCs and showed a gradual increase upon treatment with pro-inflammatory cytokines. Conclusions: We suggest that chemokines, including SCYA-25, SCYA-28, IL-8, CXCL-16 and SDF-1 can be useful in repairing damaged articular cartilage.

참고문헌 (39)

  1. Hunter W, "Of the structure and disease of articulating cartilages", Philos Trans R Soc Lond, 42, pp.514~521 (1995)
  2. Buckwalter JA, "Articular cartilage repair and transplantation", Arthritis Rheum, 41, pp.1331~1342 (1998)
  3. Pridie K, "A method of resurfacing osteoarthritis knee joints", J Bone Joint Surg Br, 41, pp.618~619 (1959)
  4. Steadman JR, "The microfracture technic in the management of complete cartilage defects in the knee joint", Orthopade, 28, pp.26~32 (1999)
  5. Brittberg M, "Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation", N Engl J Med, 331, pp.889~895 (1994)
  6. Pelttari K, "Secretion of matrix metalloproteinase 3 by expanded articular chondrocytes as a predictor of ectopic cartilage formation capacity in vivo", Arthritis Rheum, 58, pp.467~474 (2008)
  7. Kessler MW, "Emerging technologies and fourth generation issues in cartilage repair", Sports Med Arthrosc, 16, pp.246~254 (2008)
  8. DeLise AM, "Cellular interactions and signaling in cartilage development", Osteoarthritis Cartilage, 8, pp.309~334 (2000)
  9. Dickhut A, "Chondrogenesis of mesenchymal stem cells in gel-like biomaterials in vitro and in vivo", Front Biosci, 13, pp.4517~4528 (2008)
  10. Steck E, "Mesenchymal stem cell differentiation in an experimental cartilage defect: restriction of hypertrophy to bone-close neocartilage", Stem Cells Dev, 18, pp.969~978 (2009)
  11. Zhao LR, "Human bone marrow stem cells exhibit neural phenotypes and ameliorate neurological deficits after grafting into the ischemic brain of rats", Exp Neurol, 174, pp.11~20 (2002)
  12. Jin HK, "Intracerebral transplantation of mesenchymal stem cells into acid sphingomyelinase deficient mice delays the onset of neurological abnormalities and extends their life span", J Clin Invest, 109, pp.1183~1191 (2002)
  13. Turgeman G, "Engineered human mesen chymal stem cells: a novel platform for skeletal cell mediated gene therapy", J Gene Med, 3, pp.240~251 (2001)
  14. Lapidot T, "How do stem cells find their way home", Blood, 106, pp.1901~1910 (2005)
  15. Frenette PS, "Endothelial selectins and vascular cell adhesion molecule-1 promote hematopoietic progenitor homing to bone marrow", Proc Natl Acad Sci USA, 95, pp.14423~14428 (1998)
  16. Papayannopoulou T, "Molecular pathways in bone marrow homing: dominant role of a(4)b(1) over b(2)-integrins and selectins", Blood, 98, pp.2403~2411 (2001)
  17. Lapidot T, "The essential roles of the chemokine SDF-1 and its receptor CXCR4 in human stem cell homing and repopulation of transplanted immune-deficient NOD", SCID and NOD, B2m (null) mice, pp.Leukemia, 2002[DOI]
  18. Baggiolini M, "Chemokines in pathology and medicine", J Intern Med, 250, pp.91~104 (2001)
  19. Luster AD, "Chemokines—chemotactic cytokines that mediate inflammation", N Engl J Med, 338, pp.436~445 (1998)
  20. Rollins BJ, "Chemokines", Blood, 90, pp.909~928 (1997)
  21. Richard H, "Chemokine receptors", Cytokine and Growth Factor Reviews, 12, pp.313~335 (2001)
  22. Ponte AL, "The in vitro migration capacity of human bone marrow mesenchymal stem cells: comparison of chemokine and growth factor chemotactic activities", Stem Cells, 25, pp.1737~1745 (2007)
  23. Sasaki M, "Mesenchymal stem cells are recruited into wounded skin and contribute to wound repair by transdifferentiation into multiple skin cell type", J Immunol, 15, pp.2581~2587 (2008)
  24. Buckwalter JA, "Osteoarthritis and articular cartilage use, disuse and abuse: Experimental studies", J Rheumatol, 22, pp.13~15 (1995)
  25. Buckwalter JA, "Synovial joint degeneration and the syndrome of osteoarthritis", Instr Course Lect, 49, pp.481~489 (2000)
  26. Flynn JM, "Osteoarticular allografts to treat distal femoral osteonecrosis", Clin Orthop, 303, pp.38~43 (1994)
  27. Garrett JC, "Fresh osteochondral allografts for treatment of articular defects in osteochondritis dissecans of the lateral femoral condyle in adults", Clin Orthop, 303, pp.33~37 (1994)
  28. Steadman JR, "Microfracture technique for full-thickness chondral defects: Technique and clinical results", Oper Tech Orthop, 7, pp.294~299 (1997)
  29. Buckwalter JA, "Cartilage researchers tell progress: Technologies hold promise, but caution urged", Am Acad Orthop Surg Bull, 44, pp.24~26 (1996)
  30. Buckwalter JA, "Operative treatment of osteoarthrosis: Current practice and future development", J Bone Joint Surg, 76, pp.1405~1418 (1994)
  31. Buckwalter JA, "Articular cartilage II: Degeneration and osteoarthrosis, repair, regeneration and transplantation", J Bone Joint Surg, 79, pp.612~632 (1997)
  32. Pittenger MF, "Multi lineage potential of adult human mesenchymal stem cells", Science, 284, pp.143~147 (1999)
  33. Borzì RM, "Chemokines in Cartilage Degradation", Clin Orthop Relat Res, 427, pp.53~61 (2004)
  34. Jiang Y, "Pluripotency of mesenchymal stem cells derived from adult marrow", Nature, 418, pp.41~49 (2002)
  35. Badiavas EV, "Participation of bone marrowderived cells in cutaneous wound healing", J Cell Physiol, 196, pp.245~250 (2003)
  36. Inokuma D, "CTACK", CCL27 accelerates skin regeneration via accumulation of bone marrowderived keratinocytes, 2006, pp.24, 2810~2816
  37. Proudfoot AE, "Chemokine receptors: multifaceted therapeutic targets", Nat Rev Immunol, 2, pp.106~115 (2002)
  38. Lotz M, "Cartilage and joint inflammation. Regulation of IL-8 expression by human articular chondrocytes", J Immunol, 148, pp.466~473 (1992)
  39. Koç ON, "Rapid hematopoietic recovery after coinfusion of autologousblood stem cells and culture-expanded marrow mesenchymal stem cells in advanced breast cancer patients receiving high-dose chemotherapy", J Clin Oncol, 18, pp.307~316 (2000)

관련 논문AI추천

Soluble CCR2-Expressing Mesenchymal Stem Cells Inhibit Osteoarthritis Development and Progression김석중, 나현식, 조미라, Cho Keun-Hyung, Go Eun Jeong, Han Se Gyeong, Kim Seon Ae, Lee A Ram, Lee Dong Hwan, Lee Jeong Su, Lee Seon-young, Lee Yeon Su, Um In Gyu대한면역학회 · Immune Network2025 · 제25권 제3호임상적용을 위한 세포치료제로서의 성체 중간엽줄기세포송인환영남대학교 의과대학 · Journal of Yeungnam Medical Science2009 · 제26권 제1호Current perspectives in stem cell therapies for osteoarthritis of the knee김기범, 손욱진영남대학교 의과대학 · Journal of Yeungnam Medical Science2020 · 제37권 제3호줄기세포를 이용한 골관절염 치료남유준, 임예리, 주지현대한내과학회 · 대한내과학회지2019 · 제94권 제2호Intra-Articular Injection of Bone Marrow-Derived Mesenchymal Stem Cells Leading to Better Clinical Outcomes without Difference in MRI Outcomes from Baseline in Patients with Knee Osteoarthritis김희선, 이선희, Jung Ro Yoon, Young­Soo Shin대한슬관절학회 · Knee Surgery and Related Research2018 · 제30권 제3호Mesenchymal Stem Cells Isolated from the Anterior Cruciate Ligament: Characterization and Comparison of Cells from Young and Old DonorsAndre Steinert, Christian Konrads, Franz Jakob, Jakob Sieker, Ludger Klein­Hitpass, Manuela Kunz, Patrick Prager, Regina Ebert, Thomas Barthel대한슬관절학회 · Knee Surgery and Related Research2018 · 제30권 제3호

이 간행물의 다른 논문 (15건)