P Orth1, M Cucchiarini2, S Wagenpfeil3, M D Menger4, H Madry5. 1. Center of Experimental Orthopaedics, Saarland University, Homburg/Saar, Germany; Department of Orthopaedic Surgery, Saarland University Medical Center, Homburg/Saar, Germany. Electronic address: patrick.orth@uks.eu. 2. Center of Experimental Orthopaedics, Saarland University, Homburg/Saar, Germany. Electronic address: mmcucchiarini@hotmail.com. 3. Institute of Medical Biometry, Epidemiology and Medical Informatics, Saarland University Medical Center, Homburg/Saar, Germany. Electronic address: imbei@med-imbei.uni-saarland.de. 4. Institute for Clinical and Experimental Surgery, Saarland University Medical Center, Saarland University, Homburg/Saar, Germany. Electronic address: michael.menger@uks.eu. 5. Center of Experimental Orthopaedics, Saarland University, Homburg/Saar, Germany; Department of Orthopaedic Surgery, Saarland University Medical Center, Homburg/Saar, Germany. Electronic address: henning.madry@uks.eu.
Abstract
OBJECTIVE: To test the hypothesis that changes in the subchondral bone induced by parathyroid hormone (PTH [1-34]) reciprocally affect the integrity of the articular cartilage within a naïve osteochondral unit in vivo. DESIGN: Daily subcutaneous injections of 10 μg PTH [1-34]/kg were given to adult rabbits for 6 weeks, controls received saline. Blood samples were continuously collected to monitor renal function. The subchondral bone plate and subarticular spongiosa of the femoral heads were separately assessed by micro-computed tomography. Articular cartilage was evaluated by macroscopic and histological osteoarthritis scoring, polarized light microscopy, and immunohistochemical determination of type-I, type-II, type-X collagen contents, PTH [1-34] receptor and caspase-3 expression. Absolute and relative extents of hyaline and calcified articular cartilage layers were measured histomorphometrically. The correlation between PTH-induced changes in subchondral bone and articular cartilage was determined. RESULTS: PTH [1-34] enhanced volume, mineral density, and trabecular thickness within the subarticular spongiosa, and increased thickness of the calcified cartilage layer (all P < 0.05). Moreover, PTH [1-34] led to cartilage surface irregularities and reduced matrix staining (both P < 0.03). These early osteoarthritic changes correlated with and were ascribed to the increased thickness of the calcified cartilage layer (P = 0.026) and enhanced mineral density of the subarticular spongiosa (P = 0.001). CONCLUSIONS: Modifications of the subarticular spongiosa by PTH [1-34] cause broadening of the calcified cartilage layer, resulting in osteoarthritic cartilage degeneration. These findings identify a mechanism by which PTH-induced alterations of the normal subchondral bone microarchitecture may provoke early osteoarthritis.
OBJECTIVE: To test the hypothesis that changes in the subchondral bone induced by parathyroid hormone (PTH [1-34]) reciprocally affect the integrity of the articular cartilage within a naïve osteochondral unit in vivo. DESIGN: Daily subcutaneous injections of 10 μg PTH [1-34]/kg were given to adult rabbits for 6 weeks, controls received saline. Blood samples were continuously collected to monitor renal function. The subchondral bone plate and subarticular spongiosa of the femoral heads were separately assessed by micro-computed tomography. Articular cartilage was evaluated by macroscopic and histological osteoarthritis scoring, polarized light microscopy, and immunohistochemical determination of type-I, type-II, type-X collagen contents, PTH [1-34] receptor and caspase-3 expression. Absolute and relative extents of hyaline and calcified articular cartilage layers were measured histomorphometrically. The correlation between PTH-induced changes in subchondral bone and articular cartilage was determined. RESULTS:PTH [1-34] enhanced volume, mineral density, and trabecular thickness within the subarticular spongiosa, and increased thickness of the calcified cartilage layer (all P < 0.05). Moreover, PTH [1-34] led to cartilage surface irregularities and reduced matrix staining (both P < 0.03). These early osteoarthritic changes correlated with and were ascribed to the increased thickness of the calcified cartilage layer (P = 0.026) and enhanced mineral density of the subarticular spongiosa (P = 0.001). CONCLUSIONS: Modifications of the subarticular spongiosa by PTH [1-34] cause broadening of the calcified cartilage layer, resulting in osteoarthritic cartilage degeneration. These findings identify a mechanism by which PTH-induced alterations of the normal subchondral bone microarchitecture may provoke early osteoarthritis.
Authors: B M Willie; T Pap; C Perka; C O Schmidt; F Eckstein; A Arampatzis; H-C Hege; H Madry; A Vortkamp; G N Duda Journal: Z Rheumatol Date: 2015-09 Impact factor: 1.372
Authors: Marcelo Batista Bonadio; Pedro Nogueira Giglio; Camilo Partezani Helito; José Ricardo Pécora; Gilberto Luis Camanho; Marco Kawamura Demange Journal: Rev Bras Ortop Date: 2017-04-28