The Journal of Bone and Joint Surgery, Vol 75, Issue 4 532-553, Copyright © 1993 by Journal of Bone and Joint Surgery, Inc

JOURNAL CONTENTS

Cell origin and differentiation in the repair of full-thickness defects of articular cartilage

F Shapiro, S Koide and MJ Glimcher
Department of Orthopaedic Surgery, Children's Hospital, Boston, Massachusetts 02115.

The origin and differentiation of cells in the repair of three-millimeter-diameter, cylindrical, full-thickness drilled defects of articular cartilage were studied histologically in New Zealand White rabbits. The animals were allowed to move freely after the operation. Three hundred and sixty-four individual defects from 122 animals were examined as long as forty-eight weeks postoperatively. In the first few days, fibrinous arcades were established across the defect, from surface edge to surface edge, and this served to orient mesenchymal cell ingrowth along the long axes. The first evidence of synthesis of a cartilage extracellular matrix, as defined by safranin-O staining, appeared at ten days. At two weeks, cartilage was present immediately beneath the surface of collagenous tissue that was rich in flattened fibrocartilaginous cells in virtually all specimens. At three weeks, the sites of almost all of the defects had a well demarcated layer of cartilage containing chondrocytes. An essentially complete repopulation of the defects occurred at six, eight, ten, and twelve weeks, with progressive differentiation of cells to chondroblasts, chondrocytes, and osteoblasts and synthesis of cartilage and bone matrices in their appropriate locations. At twenty-four weeks, both the tidemark and the compact lamellar subchondral bone plate had been re-established. The cancellous woven bone that had formed initially in the depths of the defect was replaced by lamellar, coarse cancellous bone. Autoradiography after labeling with 3H-thymidine and 3H-cytidine demonstrated that chondrocytes from the residual adjacent articular cartilage did not participate in the repopulation of the defect. The repair was mediated wholly by the proliferation and differentiation of mesenchymal cells of the marrow. Intra-articular injections of 3H-thymidine seven days after the operation clearly labeled this mesenchymal cell pool. The label, initially taken up by undifferentiated mesenchymal cells, progressively appeared in fibroblasts, osteoblasts, articular chondroblasts, and chondrocytes, indicating their origin from the primitive mesenchymal cells of the marrow. Early traces of degeneration of the cartilage matrix were seen in many defects at twelve to twenty weeks, with the prevalence and intensity of the degeneration increasing at twenty-four, thirty-six, and forty-eight weeks. Polarized light microscopy demonstrated failure of the newly synthesized repair matrix to become adherent to, and integrated with, the cartilage immediately adjacent to the drill-hole, even when light microscopy had shown apparent continuity of the tissue. In many instances, a clear gap was seen between repair and residual cartilage.(ABSTRACT TRUNCATED AT 400 WORDS)
CiteULike    Connotea    Del.icio.us    Technorati    What's this?

This article has been cited by other articles:

				S. J. Walsh, M. J. Boyle, and V. Morganti Large Osteochondral Fractures of the Lateral Femoral Condyle in the Adolescent: Outcome of Bioabsorbable Pin Fixation J. Bone Joint Surg. Am., July 1, 2008; 90(7): 1473 - 1478. [Abstract] [Full Text] [PDF]

				A. K. Amin, J. S. Huntley, P. G. Bush, A. H. R.W. Simpson, and A. C. Hall Osmolarity Influences Chondrocyte Death in Wounded Articular Cartilage J. Bone Joint Surg. Am., July 1, 2008; 90(7): 1531 - 1542. [Abstract] [Full Text] [PDF]

				P. C. Kreuz, M. Steinwachs, C. Erggelet, A. Lahm, S. Krause, C. Ossendorf, D. Meier, N. Ghanem, and M. Uhl Importance of Sports in Cartilage Regeneration After Autologous Chondrocyte Implantation: A Prospective Study With a 3-Year Follow-up Am. J. Sports Med., August 1, 2007; 35(8): 1261 - 1268. [Abstract] [Full Text] [PDF]

				R. U. Kleemann, H. Schell, M. Thompson, D. R. Epari, G. N. Duda, and A. Weiler Mechanical Behavior of Articular Cartilage After Osteochondral Autograft Transfer in an Ovine Model Am. J. Sports Med., April 1, 2007; 35(4): 555 - 563. [Abstract] [Full Text] [PDF]

				J. Grady and D. Hughes Arthroscopic management of talar dome lesions using a transmalleolar approach. J Am Podiatr Med Assoc, May 1, 2006; 96(3): 260 - 263. [Abstract] [Full Text] [PDF]

				R. T. Burks, P. E. Greis, S. P. Arnoczky, and C. Scher The Use of a Single Osteochondral Autograft Plug in the Treatment of a Large Osteochondral Lesion in the Femoral Condyle: An Experimental Study in Sheep Am. J. Sports Med., February 1, 2006; 34(2): 247 - 255. [Abstract] [Full Text] [PDF]

				C. D. Hoemann, M. Hurtig, E. Rossomacha, J. Sun, A. Chevrier, M. S. Shive, and M. D. Buschmann Chitosan-Glycerol Phosphate/Blood Implants Improve Hyaline Cartilage Repair in Ovine Microfracture Defects J. Bone Joint Surg. Am., December 1, 2005; 87(12): 2671 - 2686. [Abstract] [Full Text] [PDF]

				E. J. Strauss, L. R. Goodrich, C.-T. Chen, C. Hidaka, and A. J. Nixon Biochemical and Biomechanical Properties of Lesion and Adjacent Articular Cartilage After Chondral Defect Repair in an Equine Model Am. J. Sports Med., November 1, 2005; 33(11): 1647 - 1653. [Abstract] [Full Text] [PDF]

				R. B. Jakobsen, L. Engebretsen, and J. R. Slauterbeck An Analysis of the Quality of Cartilage Repair Studies J. Bone Joint Surg. Am., October 1, 2005; 87(10): 2232 - 2239. [Abstract] [Full Text] [PDF]

				K. Mithoefer, R. J. Williams III, R. F. Warren, H. G. Potter, C. R. Spock, E. C. Jones, T. L. Wickiewicz, and R. G. Marx The Microfracture Technique for the Treatment of Articular Cartilage Lesions in the Knee. A Prospective Cohort Study J. Bone Joint Surg. Am., September 1, 2005; 87(9): 1911 - 1920. [Abstract] [Full Text] [PDF]

				T. Yanai, T. Ishii, F. Chang, and N. Ochiai Repair of large full-thickness articular cartilage defects in the rabbit: THE EFFECTS OF JOINT DISTRACTION AND AUTOLOGOUS BONE-MARROW-DERIVED MESENCHYMAL CELL TRANSPLANTATION J Bone Joint Surg Br, May 1, 2005; 87-B(5): 721 - 729. [Abstract] [Full Text] [PDF]

				T. J. Gill, P. C. McCulloch, S. S. Glasson, T. Blanchet, and E. A. Morris Chondral Defect Repair After the Microfracture Procedure: A Nonhuman Primate Model Am. J. Sports Med., May 1, 2005; 33(5): 680 - 685. [Abstract] [Full Text] [PDF]

				E. K. Nam, M. Makhsous, J. Koh, M. Bowen, G. Nuber, and L.-Q. Zhang Biomechanical and Histological Evaluation of Osteochondral Transplantation in a Rabbit Model Am. J. Sports Med., March 1, 2004; 32(2): 308 - 316. [Abstract] [Full Text] [PDF]

				T. Okamoto, Y. Yamamoto, M. Gotoh, C.-L. Huang, T. Nakamura, Y. Shimizu, Y. Tabata, and H. Yokomise Slow release of bone morphogenetic protein 2 from a gelatin sponge to promote regeneration of tracheal cartilage in a canine model J. Thorac. Cardiovasc. Surg., February 1, 2004; 127(2): 329 - 334. [Abstract] [Full Text] [PDF]

				E. B. Hunziker and T. M. Quinn Surgical Removal of Articular Cartilage Leads to Loss of Chondrocytes from Cartilage Bordering the Wound Edge J. Bone Joint Surg. Am., April 28, 2003; 85(90002): 85 - 92. [Abstract] [Full Text]

				T. Tallheden, J. E. Dennis, D. P. Lennon, E. Sjogren-Jansson, A. I. Caplan, and A. Lindahl Phenotypic Plasticity of Human Articular Chondrocytes J. Bone Joint Surg. Am., April 28, 2003; 85(90002): 93 - 100. [Abstract] [Full Text]

				D. A. Grande, J. Mason, E. Light, and D. Dines Stem Cells as Platforms for Delivery of Genes to Enhance Cartilage Repair J. Bone Joint Surg. Am., April 28, 2003; 85(90002): 111 - 116. [Abstract] [Full Text]

				S. A. Hunt, L. M. Jazrawi, and O. H. Sherman Arthroscopic Management of Osteoarthritis of the Knee J. Am. Acad. Ortho. Surg., September 1, 2002; 10(5): 356 - 363. [Abstract] [Full Text] [PDF]

				K F Almqvist, L Wang, J Wang, D Baeten, M Cornelissen, R Verdonk, E M Veys, and G Verbruggen Culture of chondrocytes in alginate surrounded by fibrin gel: characteristics of the cells over a period of eight weeks Ann Rheum Dis, August 1, 2001; 60(8): 781 - 790. [Abstract] [Full Text] [PDF]

				J. J. Minguell, A. Erices, and P. Conget Mesenchymal Stem Cells Experimental Biology and Medicine, June 1, 2001; 226(6): 507 - 520. [Abstract] [Full Text] [PDF]

				R. M. Hembry, J. Dyce, I. Driesang, E. B. Hunziker, A. J. Fosang, J. A. Tyler, and G. Murphy Immunolocalization of Matrix Metalloproteinases in Partial-Thickness Defects in Pig Articular Cartilage : A Preliminary Report J. Bone Joint Surg. Am., June 1, 2001; 83(6): 826 - 838. [Abstract] [Full Text]

				C. S. Ahmad, Z. A. Cohen, W. N. Levine, G. A. Ateshian, and V. C. Mow Biomechanical and Topographic Considerations for Autologous Osteochondral Grafting in the Knee Am. J. Sports Med., March 1, 2001; 29(2): 201 - 206. [Abstract] [Full Text] [PDF]

				D. W. Jackson, P. A. Lalor, H. M. Aberman, and T. M. Simon Spontaneous Repair of Full-Thickness Defects of Articular Cartilage in a Goat Model : A Preliminary Study J. Bone Joint Surg. Am., January 1, 2001; 83(1): 53 - 53. [Abstract] [Full Text]

				R. S. SELLERS, R. ZHANG, S. S. GLASSON, H. D. KIM, D. PELUSO, D. A. D'AUGUSTA, K. BECKWITH, and E. A. MORRIS Repair of Articular Cartilage Defects One Year After Treatment with Recombinant Human Bone Morphogenetic Protein-2 (rhBMP-2) J. Bone Joint Surg. Am., February 1, 2000; 82(2): 151 - 60. [Abstract] [Full Text]

				J. U. YOO, T. S. BARTHEL, K. NISHIMURA, L. SOLCHAGA, A. I. CAPLAN, V. M. GOLDBERG, and B. JOHNSTONE The Chondrogenic Potential of Human Bone-Marrow-Derived Mesenchymal Progenitor Cells J. Bone Joint Surg. Am., December 1, 1998; 80(12): 1745 - 57. [Abstract] [Full Text]

				A. P. Newman Articular Cartilage Repair Am. J. Sports Med., March 1, 1998; 26(2): 309 - 324. [Abstract] [Full Text] [PDF]

				R. S. SELLERS, D. PELUSO, and E. A. MORRIS The Effect of Recombinant Human Bone Morphogenetic Protein-2 (rhBMP-2) on the Healing of Full-Thickness Defects of Articular Cartilage J. Bone Joint Surg. Am., October 1, 1997; 79(10): 1452 - 63. [Abstract] [Full Text]

				S. A. LIETMAN, M. YANAGISHITA, T. K. SAMPATH, and A. H. REDDI Stimulation of Proteoglycan Synthesis in Explants of Porcine Articular Cartilage by Recombinant Osteogenic Protein-1 (Bone Morphogenetic Protein-7) J. Bone Joint Surg. Am., August 1, 1997; 79(8): 1132 - 7. [Abstract] [Full Text]

				J. A. BUCKWALTER and H. J. MANKIN Instructional Course Lectures, The American Academy of Orthopaedic Surgeons - Articular Cartilage. Part II: Degeneration and Osteoarthrosis, Repair, Regeneration, and Transplantation*{{dagger}} J. Bone Joint Surg. Am., April 1, 1997; 79(4): 612 - 32. [Full Text]

				C. Xue, M. Takahashi, T. Hasunuma, H. Aono, K. Yamamoto, S. Yoshino, T. Sumida, and K. Nishioka Characterisation of fibroblast-like cells in pannus lesions of patients with rheumatoid arthritis sharing properties of fibroblasts and chondrocytes Ann Rheum Dis, April 1, 1997; 56(4): 262 - 267. [Abstract] [Full Text]

				E. B. HUNZIKER and L. C. ROSENBERG Repair of Partial-Thickness Defects in Articular Cartilage: Cell Recruitment from the Synovial Membrane J. Bone Joint Surg. Am., May 1, 1996; 78(5): 721 - 33. [Abstract] [Full Text]