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

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.

Human Fat-Derived Mesenchymal Stem Cells Xenogenically Implanted in a Rat Model Show Enhanced New Bone Formation in Maxillary Alveolar Tooth Defects

“…Though alizarin red staining is considered to be the gold standard to evaluate in vitro osteogenesis, it could not be used in this study due to nonspecific absorbance of the stain by Gelfoam®, and as a result, evaluation was carried out utilizing the expression of osteogenic-specific genes to confirm cell adhesion and osteogenic differentiation. OPN is known to be expressed in osteoblasts during bone formation and remodeling [30]. RUNX2 is a transcription factor that is expressed during osteoblast differentiation and potentially upregulates the expression of bone matrix proteins [31].…”

Potential efficacy of gut microbiome dysbiosis on alleviation the progress of osteoarthritis in mice

“…The role of osteocalcin in bone remodeling, speci c expression and regulation in osteoblasts which is important biomarker in osteoporosis and level of reduced Osteocalcin expression were maintained in human osteoarthritic chondrocytes and represented a suitable biomarker of osteoarthritic chondrocyte activation [63]. Wagatsuma et.al found that diversity of gut microbiota affecting serum level of osteocalcin in patient [64].…”

Transglutaminase 2 in cartilage homoeostasis: novel links with inflammatory osteoarthritis

“…TG2 could also be involved as cystamine displays high specificity towards inhibiting TG2 transamination activity (Siegel and Khosla 2007 ). Future studies should, therefore, address TG2 functions within inflamed OA joint, taking into account the role of synovial membrane and subchondral bone into consideration despite evidence suggesting TG2 mainly as an appropriate marker of hypertrophic chondrocytes but not upregulated in the remodelled trabecular bone of OA patients (Tarquini et al 2016 ). Recent findings demonstrating the role of P2X7 receptor-dependent pore formation in TG2 externalisation (Adamczyk et al 2015 ) might be relevant in the context of TG2 secretion from activated synovial macrophages.…”