J Knee Surg 2012; 25(02): 085-098
DOI: 10.1055/s-0032-1319782
Special Focus Section
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

The Cartilage-Bone Interface

Caroline D. Hoemann
1   Department of Chemical Engineering, Ecole Polytechnique, Montreal, Quebec, Canada
2   Institute of Biomedical Engineering, Ecole Polytechnique, Montreal, Quebec, Canada
3   Groupe de Recherche en Sciences et Technologies Biomédicales (GRSTB), Ecole Polytechnique, Montreal, Quebec, Canada
,
Charles-Hubert Lafantaisie-Favreau
2   Institute of Biomedical Engineering, Ecole Polytechnique, Montreal, Quebec, Canada
,
Viorica Lascau-Coman
1   Department of Chemical Engineering, Ecole Polytechnique, Montreal, Quebec, Canada
3   Groupe de Recherche en Sciences et Technologies Biomédicales (GRSTB), Ecole Polytechnique, Montreal, Quebec, Canada
,
Gaoping Chen
1   Department of Chemical Engineering, Ecole Polytechnique, Montreal, Quebec, Canada
,
Jessica Guzmán-Morales
1   Department of Chemical Engineering, Ecole Polytechnique, Montreal, Quebec, Canada
› Author Affiliations
Further Information

Publication History

21 November 2011

26 March 2012

Publication Date:
28 June 2012 (online)

Abstract

In the knee joint, the purpose of the cartilage-bone interface is to maintain structural integrity of the osteochondral unit during walking, kneeling, pivoting, and jumping–during which tensile, compressive, and shear forces are transmitted from the viscoelastic articular cartilage layer to the much stiffer mineralized end of the long bone. Mature articular cartilage is integrated with subchondral bone through a ~20 to ~250 µm thick layer of calcified cartilage. Inside the calcified cartilage layer, perpendicular chondrocyte-derived collagen type II fibers become structurally cemented to collagen type I osteoid deposited by osteoblasts. The mature mineralization front is delineated by a thin ~5 µm undulating tidemark structure that forms at the base of articular cartilage. Growth plate cartilage is anchored to epiphyseal bone, sometimes via a thin layer of calcified cartilage and tidemark, while the hypertrophic edge does not form a tidemark and undergoes continual vascular invasion and endochondral ossification (EO) until skeletal maturity upon which the growth plates are fully resorbed and replaced by bone. In this review, the formation of the cartilage-bone interface during skeletal development and cartilage repair, and its structure and composition are presented. Animal models and human anatomical studies show that the tidemark is a dynamic structure that forms within a purely collagen type II-positive and collagen type I-negative hyaline cartilage matrix. Cartilage repair strategies that elicit fibrocartilage, a mixture of collagen type I and type II, are predicted to show little tidemark/calcified cartilage regeneration and to develop a less stable repair tissue-bone interface. The tidemark can be regenerated through a bone marrow-driven growth process of EO near the articular surface.

 
  • References

  • 1 Sasano Y, Mizoguchi I, Kagayama M, Shum L, Bringas Jr P, Slavkin HC. Distribution of type I collagen, type II collagen and PNA binding glycoconjugates during chondrogenesis of three distinct embryonic cartilages. Anat Embryol (Berl) 1992; 186 (3) 205-213
  • 2 Craig FM, Bentley G, Archer CW. The spatial and temporal pattern of collagens I and II and keratan sulphate in the developing chick metatarsophalangeal joint. Development 1987; 99 (3) 383-391
  • 3 Olsen BR, Reginato AM, Wang W. Bone development. Annu Rev Cell Dev Biol 2000; 16 (10810706) 191-220
  • 4 Sandberg M, Vuorio E. Localization of types I, II, and III collagen mRNAs in developing human skeletal tissues by in situ hybridization. J Cell Biol 1987; 104 (4) 1077-1084
  • 5 Shapiro F. Bone development and its relation to fracture repair. The role of mesenchymal osteoblasts and surface osteoblasts. Eur Cell Mater 2008; 15: 53-76
  • 6 Hunziker EB. The elusive path to cartilage regeneration. Adv Mater (Deerfield Beach Fla) 2009; 21 (32-33) 3419-3424
  • 7 Gilmore RS, Palfrey AJ. A histological study of human femoral condylar articular cartilage. J Anat 1987; 155: 77-85
  • 8 Leboy PS, Vaias L, Uschmann B, Golub E, Adams SL, Pacifici M. Ascorbic acid induces alkaline phosphatase, type X collagen, and calcium deposition in cultured chick chondrocytes. J Biol Chem 1989; 264 (29) 17281-17286
  • 9 Clark JM. The structure of vascular channels in the subchondral plate. J Anat 1990; 171: 105-115
  • 10 Haines RW. The histology of epiphyseal union in mammals. J Anat 1975; 120 (Pt 1) 1-25
  • 11 D'Angelo M, Yan Z, Nooreyazdan M , et al. MMP-13 is induced during chondrocyte hypertrophy. J Cell Biochem 2000; 77 (4) 678-693
  • 12 Sakiyama H, Inaba N, Toyoguchi T , et al. Immunolocalization of complement C1s and matrix metalloproteinase 9 (92kDa gelatinase/type IV collagenase) in the primary ossification center of the human femur. Cell Tissue Res 1994; 277 (2) 239-245
  • 13 Stickens D, Behonick DJ, Ortega N , et al. Altered endochondral bone development in matrix metalloproteinase 13-deficient mice. Development 2004; 131 (23) 5883-5895
  • 14 Little CB, Meeker CT, Hembry RM , et al. Matrix metalloproteinases are not essential for aggrecan turnover during normal skeletal growth and development. Mol Cell Biol 2005; 25 (8) 3388-3399
  • 15 Vu TH, Shipley JM, Bergers G , et al. MMP-9/gelatinase B is a key regulator of growth plate angiogenesis and apoptosis of hypertrophic chondrocytes. Cell 1998; 93 (3) 411-422
  • 16 Reich A, Jaffe N, Tong A , et al. Weight loading young chicks inhibits bone elongation and promotes growth plate ossification and vascularization. J Appl Physiol 2005; 98 (6) 2381-2389
  • 17 Farnum CE, Lee AO, O'Hara K, Wilsman NJ. Effect of short-term fasting on bone elongation rates: an analysis of catch-up growth in young male rats. Pediatr Res 2003; 53 (1) 33-41
  • 18 Kim HK, Su P-H, Qiu Y-S. Histopathologic changes in growth-plate cartilage following ischemic necrosis of the capital femoral epiphysis. An experimental investigation in immature pigs. J Bone Joint Surg Am 2001; 83-A (5) 688-697
  • 19 Alini M, Matsui Y, Dodge GR, Poole AR. The extracellular matrix of cartilage in the growth plate before and during calcification: changes in composition and degradation of type II collagen. Calcif Tissue Int 1992; 50 (4) 327-335
  • 20 Cackowski FC, Anderson JL, Patrene KD , et al. Osteoclasts are important for bone angiogenesis. Blood 2010; 115 (1) 140-149
  • 21 Chen G, Sun J, Lascau-Coman V, Chevrier A, Marchand C, Hoemann CD. Acute osteoclast activity following subchondral drilling is promoted by chitosan and associated with improved cartilage tissue integration. Cartilage 2011; 2: 173-185
  • 22 Hashimoto S, Ochs RL, Rosen F , et al. Chondrocyte-derived apoptotic bodies and calcification of articular cartilage. Proc Natl Acad Sci U S A 1998; 95 (6) 3094-3099
  • 23 Hunziker EB, Kapfinger E, Geiss J. The structural architecture of adult mammalian articular cartilage evolves by a synchronized process of tissue resorption and neoformation during postnatal development. Osteoarthritis Cartilage 2007; 15 (4) 403-413
  • 24 Namba RS, Meuli M, Sullivan KM, Le AX, Adzick NS. Spontaneous repair of superficial defects in articular cartilage in a fetal lamb model. J Bone Joint Surg Am 1998; 80 (1) 4-10
  • 25 Hayes AJ, MacPherson S, Morrison H, Dowthwaite G, Archer CW. The development of articular cartilage: evidence for an appositional growth mechanism. Anat Embryol (Berl) 2001; 203 (6) 469-479
  • 26 Oegema Jr TR, Carpenter RJ, Hofmeister F, Thompson Jr RC. The interaction of the zone of calcified cartilage and subchondral bone in osteoarthritis. Microsc Res Tech 1997; 37 (4) 324-332
  • 27 Heinegård D, Oldberg A. Structure and biology of cartilage and bone matrix noncollagenous macromolecules. FASEB J 1989; 3 (9) 2042-2051
  • 28 Gannon JM, Walker G, Fischer M, Carpenter R, Thompson Jr RC, Oegema Jr TR. Localization of type X collagen in canine growth plate and adult canine articular cartilage. J Orthop Res 1991; 9 (4) 485-494
  • 29 Jiang J, Leong NL, Mung JC, Hidaka C, Lu HH. Interaction between zonal populations of articular chondrocytes suppresses chondrocyte mineralization and this process is mediated by PTHrP. Osteoarthritis Cartilage 2008; 16 (1) 70-82
  • 30 Sundaramurthy S, Mao JJ. Modulation of endochondral development of the distal femoral condyle by mechanical loading. J Orthop Res 2006; 24 (2) 229-241
  • 31 Stephens M, Kwan APL, Bayliss MT, Archer CW. Human articular surface chondrocytes initiate alkaline phosphatase and type X collagen synthesis in suspension culture. J Cell Sci 1992; 103 (Pt 4) 1111-1116
  • 32 Ali SY, Sajdera SW, Anderson HC. Isolation and characterization of calcifying matrix vesicles from epiphyseal cartilage. Proc Natl Acad Sci U S A 1970; 67 (3) 1513-1520
  • 33 Shum L, Nuckolls G. The life cycle of chondrocytes in the developing skeleton. Arthritis Res 2002; 4 (2) 94-106
  • 34 Robinson RA, Cameron DA. Electron microscopy of the primary spongiosa of the metaphysis at the distal end of the femur in the newborn infant. J Bone Joint Surg Am 1958; 40-A (3) 687-697
  • 35 Boyde A, Firth EC. Articular calcified cartilage canals in the third metacarpal bone of 2-year-old thoroughbred racehorses. J Anat 2004; 205 (6) 491-500
  • 36 Kobayashi S, Baba H, Takeno K , et al. Fine structure of cartilage canal and vascular buds in the rabbit vertebral endplate. Laboratory investigation. J Neurosurg Spine 2008; 9 (1) 96-103
  • 37 Bonde HV, Talman MLM, Kofoed H. The area of the tidemark in osteoarthritis—a three-dimensional stereological study in 21 patients. APMIS 2005; 113 (5) 349-352
  • 38 Arkill KP, Winlove CP. Solute transport in the deep and calcified zones of articular cartilage. Osteoarthritis Cartilage 2008; 16 (6) 708-714
  • 39 Pan J, Zhou XZ, Li W, Novotny JE, Doty SB, Wang LY. In situ measurement of transport between subchondral bone and articular cartilage. J Orthop Res 2009; 27 (10) 1347-1352
  • 40 Bellows CG, Aubin JE, Heersche JNM. Initiation and progression of mineralization of bone nodules formed in vitro: the role of alkaline phosphatase and organic phosphate. Bone Miner 1991; 14 (1) 27-40
  • 41 Rey C, Beshah K, Griffin R, Glimcher MJ. Structural studies of the mineral phase of calcifying cartilage. J Bone Miner Res 1991; 6 (5) 515-525
  • 42 Hoemann CD, El-Gabalawy H, McKee MD. In vitro osteogenesis assays: influence of the primary cell source on alkaline phosphatase activity and mineralization. Pathol Biol (Paris) 2009; 57 (4) 318-323
  • 43 Wang FY, Ying Z, Duan XJ , et al. Histomorphometric analysis of adult articular calcified cartilage zone. J Struct Biol 2009; 168 (3) 359-365
  • 44 Lane LB, Bullough PG. Age-related changes in the thickness of the calcified zone and the number of tidemarks in adult human articular cartilage. J Bone Joint Surg Br 1980; 62 (3) 372-375
  • 45 Müller-Gerbl M, Schulte E, Putz R. The thickness of the calcified layer of articular cartilage: a function of the load supported?. J Anat 1987; 154: 103-111
  • 46 Hunziker EB, Quinn TM, Häuselmann HJ. Quantitative structural organization of normal adult human articular cartilage. Osteoarthritis Cartilage 2002; 10 (7) 564-572
  • 47 Lyons TJ, McClure SF, Stoddart RW, McClure J. The normal human chondro-osseous junctional region: evidence for contact of uncalcified cartilage with subchondral bone and marrow spaces. BMC Musculoskelet Disord 2006; 7: 52
  • 48 Frisbie DD, Cross MW, McIlwraith CW. A comparative study of articular cartilage thickness in the stifle of animal species used in human pre-clinical studies compared to articular cartilage thickness in the human knee. Vet Comp Orthop Traumatol 2006; 19 (3) 142-146
  • 49 Madry H, van Dijk CN, Mueller-Gerbl M. The basic science of the subchondral bone. Knee Surg Sports Traumatol Arthrosc 2010; 18 (4) 419-433
  • 50 Koszyca B, Fazzalari NL, Vernon-Roberts B. Calcified cartilage, subchondral and cancellous bone morphometry within the knee of normal subjects. Knee 1996; 3: 15-22
  • 51 Burr DB, Schaffler MB. The involvement of subchondral mineralized tissues in osteoarthrosis: quantitative microscopic evidence. Microsc Res Tech 1997; 37 (4) 343-357
  • 52 Kaabar W, Iaklouk A, Bunk O, Baily M, Farquharson MJ, Bradley D. Compositional and structural studies of the bone-cartilage interface using PIXE and SAXS techniques. Nuclear Instruments & Methods in Physics Research Section Accelerators Spectrometers Detectors and Associated Equipment 2010; 619 (1–3) 78-82
  • 53 Zoeger N, Roschger P, Hofstaetter JG , et al. Lead accumulation in tidemark of articular cartilage. Osteoarthritis Cartilage 2006; 14 (9) 906-913
  • 54 Marchand C, Chen HM, Buschmann MD, Hoemann CD. Standardized three-dimensional volumes of interest with adapted surfaces for more precise subchondral bone analyses by micro-computed tomography. Tissue Eng Part C Methods 2011; 17 (4) 475-484
  • 55 Zizak I, Roschger P, Paris O , et al. Characteristics of mineral particles in the human bone/cartilage interface. J Struct Biol 2003; 141 (3) 208-217
  • 56 Duer MJ, Friscić T, Murray RC, Reid DG, Wise ER. The mineral phase of calcified cartilage: its molecular structure and interface with the organic matrix. Biophys J 2009; 96 (8) 3372-3378
  • 57 Lyons TJ, Stoddart RW, McClure SF, McClure J. The tidemark of the chondro-osseous junction of the normal human knee joint. J Mol Histol 2005; 36 (3) 207-215
  • 58 Miller LM, Novatt JT, Hamerman D, Carlson CS. Alterations in mineral composition observed in osteoarthritic joints of cynomolgus monkeys. Bone 2004; 35 (2) 498-506
  • 59 Burr DB. Anatomy and physiology of the mineralized tissues: role in the pathogenesis of osteoarthrosis. Osteoarthritis Cartilage 2004; 12 (Suppl A) S20-S30
  • 60 Marchand C, Chen G, Tran-Khanh N , et al. Microdrilled cartilage defects treated with thrombin-solidified chitosan/blood implant regenerate a more hyaline, stable, and structurally integrated osteochondral unit compared to drilled controls. Tissue Eng Part A 2012; 18 (5–6) 508-519
  • 61 Cameron ML, Briggs KK, Steadman JR. Reproducibility and reliability of the outerbridge classification for grading chondral lesions of the knee arthroscopically. Am J Sports Med 2003; 31 (1) 83-86
  • 62 Mithoefer K, McAdams TR, Scopp JM, Mandelbaum BR. Emerging options for treatment of articular cartilage injury in the athlete. Clin Sports Med 2009; 28 (1) 25-40
  • 63 Peterson L, Minas T, Brittberg M, Nilsson A, Sjögren-Jansson E, Lindahl A, Sjögren-Jansson E. Two- to 9-year outcome after autologous chondrocyte transplantation of the knee. Clin Orthop Relat Res 2000; 374 (374) 212-234
  • 64 Drobnic M, Radosavljevic D, Cör A, Brittberg M, Strazar K. Debridement of cartilage lesions before autologous chondrocyte implantation by open or transarthroscopic techniques: a comparative study using post-mortem materials. J Bone Joint Surg Br 2010; 92 (4) 602-608
  • 65 Mika J, Clanton TO, Pretzel D, Schneider G, Ambrose CG, Kinne RW. Surgical preparation for articular cartilage regeneration without penetration of the subchondral bone plate: in vitro and in vivo studies in humans and sheep. Am J Sports Med 2011; 39 (3) 624-631
  • 66 Steadman JR, Rodkey WG, Singleton SB, Briggs KK. Microfracture technique for full-thickness chondral defects: technique and clinical results. Oper Tech Orthop 1997; 7 (4) 300-304
  • 67 Mithoefer K, Williams III RJ, Warren RF , et al. The microfracture technique for the treatment of articular cartilage lesions in the knee. A prospective cohort study. J Bone Joint Surg Am 2005; 87 (9) 1911-1920
  • 68 Knutsen G, Engebretsen L, Ludvigsen TC , et al. Autologous chondrocyte implantation compared with microfracture in the knee. A randomized trial. J Bone Joint Surg Am 2004; 86-A (3) 455-464
  • 69 Hurtig MB, Buschmann MD, Fortier LA , et al. Preclinical Studies for Cartilage Repair: Recommendations from the International Cartilage Repair Society. Cartilage. 2011; 2 (2) 137-152
  • 70 Frisbie DD, Morisset S, Ho CP, Rodkey WG, Steadman JR, McIlwraith CW. Effects of calcified cartilage on healing of chondral defects treated with microfracture in horses. Am J Sports Med 2006; 34 (11) 1824-1831
  • 71 Hoemann CD, Hurtig M, Rossomacha E , et al. Chitosan-glycerol phosphate/blood implants improve hyaline cartilage repair in ovine microfracture defects. J Bone Joint Surg Am 2005; 87 (12) 2671-2686
  • 72 Hoemann CD, Kandel R, Roberts S , et al. International Cartilage Repair Society (ICRS) Recommended Guidelines for Histological Endpoints for Cartilage Repair Studies in Animal Models and Clinical Trials. Cartilage 2011; 2 (2) 153-172
  • 73 Kon E, Mutini A, Arcangeli E , et al. Novel nanostructured scaffold for osteochondral regeneration: pilot study in horses. J Tissue Eng Regen Med 2010; 4 (4) 300-308
  • 74 Shapiro F, Koide S, Glimcher MJ. Cell origin and differentiation in the repair of full-thickness defects of articular cartilage. J Bone Joint Surg Am 1993; 75 (4) 532-553
  • 75 Chevrier A, Hoemann CD, Sun J, Buschmann MD. Temporal and spatial modulation of chondrogenic foci in subchondral microdrill holes by chitosan-glycerol phosphate/blood implants. Osteoarthritis Cartilage 2011; 19 (1) 136-144
  • 76 Hoemann CD, Chen G, Marchand C , et al. Scaffold-guided subchondral bone repair: implication of neutrophils and alternatively activated arginase-1+ macrophages. Am J Sports Med 2010; 38 (9) 1845-1856
  • 77 Chevrier A, Hoemann CD, Sun J, Buschmann MD. Chitosan-glycerol phosphate/blood implants increase cell recruitment, transient vascularization and subchondral bone remodeling in drilled cartilage defects. Osteoarthritis Cartilage 2007; 15 (3) 316-327
  • 78 Chen H, Hoemann CD, Sun J , et al. Depth of subchondral perforation influences the outcome of bone marrow stimulation cartilage repair. J Orthop Res 2011; 29 (8) 1178-1184
  • 79 Insall JN. Intra-articular surgery for degenerative arthritis of the knee. A report of the work of the late K. H. Pridie. J Bone Joint Surg Br 1967; 49 (2) 211-228
  • 80 Guzmàn-Morales J, Lafantaisie-Favreau C, Sun J, Rivard G, Hoemann CD. Analysis of the mid-term effects of chitosan-NaCl/blood pre-solidified implants in an in vivo osteochondral repair model. Paper presented at: International Cartilage Repair Society, 25 Sept, 2010; Barcelona, Spain.
  • 81 Qiu YS, Shahgaldi BF, Revell WJ, Heatley FW. Observations of subchondral plate advancement during osteochondral repair: a histomorphometric and mechanical study in the rabbit femoral condyle. Osteoarthritis Cartilage 2003; 11 (11) 810-820
  • 82 Chen HM, Chevrier A, Hoemann CD, Sun J, Ouyang W, Buschmann MD. Characterization of subchondral bone repair for marrow-stimulated chondral defects and its relationship to articular cartilage resurfacing. Am J Sports Med 2011; 39 (8) 1731-1740
  • 83 Mainil-Varlet P, Van Damme B, Nesic D, Knutsen G, Kandel R, Roberts S. A new histology scoring system for the assessment of the quality of human cartilage repair: ICRS II. Am J Sports Med 2010; 38 (5) 880-890
  • 84 Saris DB, Vanlauwe J, Victor J , et al. Characterized chondrocyte implantation results in better structural repair when treating symptomatic cartilage defects of the knee in a randomized controlled trial versus microfracture. Am J Sports Med 2008; 36 (2) 235-246
  • 85 Vanlauwe J, Saris DBF, Victor J, Almqvist KF, Bellemans J, Luyten FP ; TIG/ACT/01/2000&EXT Study Group. Five-year outcome of characterized chondrocyte implantation versus microfracture for symptomatic cartilage defects of the knee: early treatment matters. Am J Sports Med 2011; 39 (12) 2566-2574
  • 86 Brittberg M, Lindahl A, Nilsson A, Ohlsson C, Isaksson O, Peterson L. Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. N Engl J Med 1994; 331 (14) 889-895
  • 87 Hoemann CD, Tran-Khan N, Méthot S , et al. Correlation of tissue histomorphometry with ICRS histology scores in biopsies obtained from a randomized controlled clinical trial comparing BST-CarGel™ versus microfracture. Paper presented at: International Cartilage Repair Society, 27 Sept, 2010; Barcelona, Spain
  • 88 Méthot S, Hoemann CD, Rossomacha E , et al. ICRS Histology Scores of Biopsies from an Interim Analysis of a Randomized Controlled Clinical Trial Show Significant Improvement in Tissue Quality at 13 Months for BST-CarGel versus Microfracture. Paper presented at: International Cartilage Repair Society, 27 Sept, 2010; Barcelona, Spain
  • 89 Changoor A, Nelea M, Méthot S , et al. Structural characteristics of the collagen network in human normal, degraded and repair articular cartilages observed in polarized light and scanning electron microscopies. Osteoarthritis Cartilage 2011; 19 (12) 1458-1468
  • 90 Roos EM, Engelhart L, Ranstam J , et al. ICRS Recommendation Document: Patient-Reported Outcome Instruments for Use in Patients with Articular Cartilage Defects. Cartilage 2011; 2 (2) 122-136
  • 91 Lascau-Coman V, Buschmann MD, Hoemann CD. Rapid EDTA Microwave Decalcification of Rabbit Osteochondral Samples Preserves Enzyme Activity and Antigen Epitopes. J Bone Miner Res 2008; 23: S408-S408
  • 92 Chevrier A, Rossomacha E, Buschmann MD, Hoemann CD. Optimization of histoprocessing methods to detect glycosaminoglycan, collagen type II, and collagen type I in decalcified rabbit osteochondral sections. J Histotechnol 2005; 28 (3) 165-175