Comparison of tissue transglutaminase 2 and bone biological markers osteocalcin, osteopontin and sclerostin expression in human osteoporosis and osteoarthritis

Amino Acids. 2017 Mar;49(3):683-693. doi: 10.1007/s00726-016-2290-4. Epub 2016 Jun 29.

Abstract

Osteoporosis (OP) and osteoarthritis (OA) are the most common joint diseases, with a high incidence in the elderly population. OP is characterized by trabecular bone remodeling and reabsorption, whereas articular cartilage and subchondral bone remodeling are major features of OA. Although classically considered as independent or even conflicting processes, clinical coexistence of OP and OA was recently described. Transglutaminase 2 (TG2) expression is considered a biomarker of OA, but its role in osteoporotic bone remodeling is still uncertain. We investigated TG2 and bone biological markers (Osteocalcin, Osteopontin, and Sclerostin) in osteoporotic and osteoarthritic osteocartilagineous tissue (n = 54) and human chondrocyte cultures in vitro by immunohistochemistry, immunofluorescence and RT-PCR. Histomorphometric evaluation of bone trabecular remodeling was also performed. In cartilage, TG2 expression was faint in control and OP and significantly less than in OA and OP + OA chondrocytes; the opposite was found for Osteocalcin, whereas Osteopontin and Sclerostin expression was similar. In the subchondral trabecular bone, osteocytes/osteoblasts TG2 expression was slight and similar comparing control, OP, OA, and OP + OA group, whereas Osteocalcin and Osteopontin expression was lower in OP compared to control, OA and OP + OA. Increased TG2 and reduced Osteocalcin expression were maintained in human osteoarthritic chondrocytes in vitro. Histomorphometric analysis confirmed reduced trabecular bone mass in OP and OP + OA compared with OA patients. TG2 represented a suitable biomarker of osteoarthritic chondrocyte activation, whereas osteocalcin and osteopontin characterized osteoporotic osteocyte/osteoblast changes; differences were lost in OP + OA patients, suggesting careful consideration when coexistence of the two diseases occurs.

Keywords: Bone remodeling; Cartilage; Osteoarthritis; Osteoporosis; Transglutaminase 2.

Publication types

  • Comparative Study

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Aged
  • Biomarkers / metabolism
  • Bone Morphogenetic Proteins / genetics
  • Bone Morphogenetic Proteins / immunology*
  • Bone and Bones / immunology
  • Bone and Bones / pathology
  • Cartilage, Articular / immunology
  • Cartilage, Articular / pathology
  • Chondrocytes / immunology
  • Chondrocytes / pathology
  • Female
  • GTP-Binding Proteins / genetics
  • GTP-Binding Proteins / immunology*
  • Gene Expression
  • Genetic Markers / genetics
  • Genetic Markers / immunology*
  • Humans
  • Male
  • Middle Aged
  • Osteoarthritis / genetics
  • Osteoarthritis / immunology*
  • Osteoarthritis / pathology
  • Osteoblasts / immunology
  • Osteoblasts / pathology
  • Osteocalcin / genetics
  • Osteocalcin / immunology*
  • Osteocytes / immunology
  • Osteocytes / pathology
  • Osteopontin / genetics
  • Osteopontin / immunology*
  • Osteoporosis / genetics
  • Osteoporosis / immunology*
  • Osteoporosis / pathology
  • Primary Cell Culture
  • Protein Glutamine gamma Glutamyltransferase 2
  • Transglutaminases / genetics
  • Transglutaminases / immunology*

Substances

  • Adaptor Proteins, Signal Transducing
  • Biomarkers
  • Bone Morphogenetic Proteins
  • Genetic Markers
  • SOST protein, human
  • SPP1 protein, human
  • TGM2 protein, human
  • Osteocalcin
  • Osteopontin
  • Protein Glutamine gamma Glutamyltransferase 2
  • Transglutaminases
  • GTP-Binding Proteins