B A Lakin1, D J Ellis2, J S Shelofsky1, J D Freedman3, M W Grinstaff4, B D Snyder5. 1. Center for Advanced Orthopaedic Studies, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Department of Biomedical Engineering, Boston University, Boston, MA, USA. 2. Center for Advanced Orthopaedic Studies, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. 3. Center for Advanced Orthopaedic Studies, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Department of Pharmacology and Experimental Therapeutics, Boston University, Boston, MA, USA. 4. Department of Biomedical Engineering, Boston University, Boston, MA, USA; Department of Chemistry, Boston University, Boston, MA, USA. Electronic address: mgrin@bu.edu. 5. Center for Advanced Orthopaedic Studies, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Department of Orthopaedic Surgery, Boston Children's Hospital, Boston, MA, USA. Electronic address: bsnyder@bidmc.harvard.edu.
Abstract
OBJECTIVE: The aim of this work is to establish the human metacarpal as a new whole joint surface early-stage osteoarthritis (OA) model that enables comparisons of articular cartilage and subchondral bone through high resolution contrast-enhanced CT (CECT) imaging, mechanical testing, and biochemical analysis. DESIGN: The fourth metacarpal was obtained from 12 human cadaveric donors and baseline μCT imaging was followed by indentation testing. The samples were then immersed in anionic (Ioxaglate) and cationic (CA4+) iodinated contrast agent solutions followed by CECT. Cartilage GAG content and distribution was measured using the 1,9 dimethylmethylene blue (DMMB) assay and Safranin-O histology staining. Linear regression was performed to compare cartilage and subchondral bone properties. RESULTS: Strong and significant positive correlations were observed between CA4+ CECT attenuation and both GAG content (R(2) = 0.86) and equilibrium modulus (R(2) = 0.84), while correlations using Ioxaglate were insignificant (R(2) ≤ 0.24, P > 0.05). Subchondral bone plate (SBP) thickness negatively and significantly correlated with SBP mineral density (R(2) = 0.49). Cartilage GAG content significantly correlated with several trabecular bone properties, including positive correlations with bone volume fraction (%BV/TV, R(2) = 0.67), trabecular number (Tb.N, R(2) = 0.60), and trabecular thickness (R(2) = 0.42), and negative relationships with structural model index (SMI, R(2) = 0.78) and trabecular spacing (Tb.Sp, R(2) = 0.56). Similarly, equilibrium modulus correlated positively with %BV/TV (R(2) = 0.50), Tb.N (R(2) = 0.59) and negatively with Tb.Sp (R(2) = 0.55) and SMI (R(2) = 0.60). CONCLUSION: This study establishes the human metacarpal as a new early-stage OA model suitable for rapid, high resolution CECT imaging, mechanical testing, and biochemical analysis of the cartilage and subchondral bone, and for examining their inter-relationships.
OBJECTIVE: The aim of this work is to establish the human metacarpal as a new whole joint surface early-stage osteoarthritis (OA) model that enables comparisons of articular cartilage and subchondral bone through high resolution contrast-enhanced CT (CECT) imaging, mechanical testing, and biochemical analysis. DESIGN: The fourth metacarpal was obtained from 12 human cadaveric donors and baseline μCT imaging was followed by indentation testing. The samples were then immersed in anionic (Ioxaglate) and cationic (CA4+) iodinated contrast agent solutions followed by CECT. Cartilage GAG content and distribution was measured using the 1,9 dimethylmethylene blue (DMMB) assay and Safranin-O histology staining. Linear regression was performed to compare cartilage and subchondral bone properties. RESULTS: Strong and significant positive correlations were observed between CA4+ CECT attenuation and both GAG content (R(2) = 0.86) and equilibrium modulus (R(2) = 0.84), while correlations using Ioxaglate were insignificant (R(2) ≤ 0.24, P > 0.05). Subchondral bone plate (SBP) thickness negatively and significantly correlated with SBP mineral density (R(2) = 0.49). Cartilage GAG content significantly correlated with several trabecular bone properties, including positive correlations with bone volume fraction (%BV/TV, R(2) = 0.67), trabecular number (Tb.N, R(2) = 0.60), and trabecular thickness (R(2) = 0.42), and negative relationships with structural model index (SMI, R(2) = 0.78) and trabecular spacing (Tb.Sp, R(2) = 0.56). Similarly, equilibrium modulus correlated positively with %BV/TV (R(2) = 0.50), Tb.N (R(2) = 0.59) and negatively with Tb.Sp (R(2) = 0.55) and SMI (R(2) = 0.60). CONCLUSION: This study establishes the human metacarpal as a new early-stage OA model suitable for rapid, high resolution CECT imaging, mechanical testing, and biochemical analysis of the cartilage and subchondral bone, and for examining their inter-relationships.
Authors: Rachel Ellman; Jordan Spatz; Alison Cloutier; Rupert Palme; Blaine A Christiansen; Mary L Bouxsein Journal: J Bone Miner Res Date: 2013-04 Impact factor: 6.741
Authors: Barbara Herz; Andreas Albrecht; Matthias Englbrecht; Götz H Welsch; Michael Uder; Nina Renner; Philipp Schlechtweg; Dominik Paul; Lars Lauer; Klaus Engelke; Rolf Janka; Jürgen Rech; Georg Schett; Stephanie Finzel Journal: Ann Rheum Dis Date: 2013-04-26 Impact factor: 19.103
Authors: M M Hyttinen; J Töyräs; T Lapveteläinen; J Lindblom; D J Prockop; S W Li; M Arita; J S Jurvelin; H J Helminen Journal: Ann Rheum Dis Date: 2001-03 Impact factor: 19.103
Authors: Charlene M Flahiff; Daria A Narmoneva; Janet L Huebner; Virginia B Kraus; Farshid Guilak; Lori A Setton Journal: J Biomech Date: 2002-09 Impact factor: 2.712
Authors: Benjamin A Lakin; Harsh Patel; Conor Holland; Jonathan D Freedman; Joshua S Shelofsky; Brian D Snyder; Kathryn S Stok; Mark W Grinstaff Journal: J Orthop Res Date: 2016-01-06 Impact factor: 3.494
Authors: Brad B Nelson; Rachel C Stewart; Chris E Kawcak; Jonathan D Freedman; Amit N Patwa; Brian D Snyder; Laurie R Goodrich; Mark W Grinstaff Journal: Cartilage Date: 2018-12-02 Impact factor: 4.634
Authors: Maleeha Mashiatulla; Meghan M Moran; Deva Chan; Jun Li; Jonathan D Freedman; Brian D Snyder; Mark W Grinstaff; Anna Plaas; Dale R Sumner Journal: J Orthop Res Date: 2017-05-23 Impact factor: 3.494
Authors: Jonathan D Freedman; Daniel J Ellis; Hrvoje Lusic; Gopal Varma; Aaron K Grant; Benjamin A Lakin; Brian D Snyder; Mark W Grinstaff Journal: J Orthop Res Date: 2019-11-14 Impact factor: 3.494
Authors: Miitu K M Honkanen; Hanna Matikka; Juuso T J Honkanen; Abhisek Bhattarai; Mark W Grinstaff; Antti Joukainen; Heikki Kröger; Jukka S Jurvelin; Juha Töyräs Journal: J Orthop Res Date: 2019-03-28 Impact factor: 3.494
Authors: Miitu K M Honkanen; Annina E A Saukko; Mikael J Turunen; Rubina Shaikh; Mithilesh Prakash; Goran Lovric; Antti Joukainen; Heikki Kröger; Mark W Grinstaff; Juha Töyräs Journal: J Orthop Res Date: 2019-10-14 Impact factor: 3.494
Authors: Abhisek Bhattarai; Janne T A Mäkelä; Behdad Pouran; Heikki Kröger; Harrie Weinans; Mark W Grinstaff; Juha Töyräs; Mikael J Turunen Journal: J Orthop Res Date: 2020-08-28 Impact factor: 3.494