Your browser doesn't support javascript.
loading
Disruption of glucocorticoid signalling in osteoblasts attenuates age-related surgically induced osteoarthritis.
Tu, J; Zhang, P; Ji, Z; Henneicke, H; Li, J; Kim, S; Swarbrick, M M; Wu, Y; Little, C B; Seibel, M J; Zhou, H.
Afiliação
  • Tu J; Bone Research Program, ANZAC Research Institute, The University of Sydeney, Sydney, NSW, Australia; Concord Clinical School, The University of Sydney, Sydney, NSW, Australia. Electronic address: jinwen.tu@sydney.edu.au.
  • Zhang P; Bone Research Program, ANZAC Research Institute, The University of Sydeney, Sydney, NSW, Australia; Department of Acupuncture, Tuina and Traumatology, The Sixth People's Hospital Affiliated to Shanghai Jiaotong University, Shanghai, China. Electronic address: pongchang@hotmail.com.
  • Ji Z; Bone Research Program, ANZAC Research Institute, The University of Sydeney, Sydney, NSW, Australia; Department of Orthopaedics, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China. Electronic address: zhej23@163.com.
  • Henneicke H; Bone Research Program, ANZAC Research Institute, The University of Sydeney, Sydney, NSW, Australia; Department of Medicine III & Center for Healthy Aging, Technische University Dresden Medical Center, Dresden, Germany; Center for Regenerative Therapies Dresden, Technische University, Dresden, Ge
  • Li J; Bone Research Program, ANZAC Research Institute, The University of Sydeney, Sydney, NSW, Australia; Key Laboratory for Space Bioscience & Biotechnology, Institute of Special Environmental Biophysics, School of Life Sciences, Northwestern Polytechnical University, Shaanxi, China. Electronic addre
  • Kim S; Bone Research Program, ANZAC Research Institute, The University of Sydeney, Sydney, NSW, Australia; Concord Clinical School, The University of Sydney, Sydney, NSW, Australia. Electronic address: sarah.kim1@sydney.edu.au.
  • Swarbrick MM; Bone Research Program, ANZAC Research Institute, The University of Sydeney, Sydney, NSW, Australia; Concord Clinical School, The University of Sydney, Sydney, NSW, Australia. Electronic address: michael.swarbrick@sydney.edu.au.
  • Wu Y; Department of Acupuncture, Tuina and Traumatology, The Sixth People's Hospital Affiliated to Shanghai Jiaotong University, Shanghai, China. Electronic address: wuyaochi63@yeah.net.
  • Little CB; Raymond Purves Laboratories, Kolling Institute and Institute of Bone and Joint Research, The University of Sydney, Royal North Shore Hospital, St. Leonards, NSW, Australia. Electronic address: christopher.little@sydney.edu.au.
  • Seibel MJ; Bone Research Program, ANZAC Research Institute, The University of Sydeney, Sydney, NSW, Australia; Concord Clinical School, The University of Sydney, Sydney, NSW, Australia; Department of Endocrinology & Metabolism, Concord Hospital, Sydney, NSW, Australia. Electronic address: markus.seibel@syd
  • Zhou H; Bone Research Program, ANZAC Research Institute, The University of Sydeney, Sydney, NSW, Australia; Concord Clinical School, The University of Sydney, Sydney, NSW, Australia. Electronic address: h.zhou@sydney.edu.au.
Osteoarthritis Cartilage ; 27(10): 1518-1525, 2019 10.
Article em En | MEDLINE | ID: mdl-31176016
ABSTRACT

OBJECTIVE:

Aging is a major risk factor for osteoarthritis (OA). Skeletal expression and activity of the glucocorticoid-activating enzyme 11ß-hydroxysteroid-dehydrogenase type 1 increases progressively with age in humans and rodents. Here we investigated the role of endogenous osteocytic and osteoblastic glucocorticoid (GC) signalling in the development of osteoarthritic bone and cartilage damage in mice.

METHODS:

We utilized transgenic (tg) mice in which glucocorticoid signalling is disrupted in osteoblasts and osteocytes via overexpression of the glucocorticoid-inactivating enzyme, 11ß-hydroxysteroid-dehydrogenase type 2. Osteoarthritis was induced in 10- and 22-week-old male transgenic mice (tg-OA, n = 6/group) and their wildtype littermates (WT-OA, n = 7-8/group) by surgical destabilization of the medial meniscus (DMM). Sham-operated mice served as controls (WT- & tg-Sham, n = 3-5 and 6-8/group at 10- and 22-weeks of age, respectively).

RESULTS:

Sixteen weeks after DMM surgery, mice developed features of cartilage degradation, subchondral bone sclerosis and osteophyte formation. These changes did not differ between WT and tg mice when OA was induced at 10-weeks of age. However, when OA was induced at 22-weeks of age, cartilage erosion was significantly attenuated in tg-OA mice compared to WT-OA littermates. Similarly, subchondral bone volume (-5.2%, 95% confidence intervals (CI) -9.1 to -1.2%, P = 0.014) and osteophyte size (-4.0 mm2, 95% CI -7.5 to -0.5 mm2, P = 0.029) were significantly reduced in tg-OA compared to WT-OA mice.

CONCLUSION:

Glucocorticoid signalling in cells of the osteoblast lineage promotes the development of surgically-induced osteoarthritis in older, but not younger, male mice. These data implicate osteoblasts and osteocytes in the progression of DMM-OA, via a glucocorticoid-dependent and age-related pathway.
Assuntos
Palavras-chave
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Osteoartrite / Osteoblastos / Glucocorticoides Tipo de estudo: Risk_factors_studies Limite: Animals Idioma: En Ano de publicação: 2019 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Osteoartrite / Osteoblastos / Glucocorticoides Tipo de estudo: Risk_factors_studies Limite: Animals Idioma: En Ano de publicação: 2019 Tipo de documento: Article