Expression of bone resorption genes in osteoarthritis and in osteoporosis

Abstract

Cathepsin K and MMP-9 are considered to be the most abundant proteases in osteoclasts. TRAP is a marker for osteoclasts, and there is increasing evidence of its proteolytic role in bone resorption. RANKL is a recently discovered regulator of osteoclast maturation and activity and induces expression of many genes. This study compared cathepsin K, MMP-9, TRAP, RANKL, OPG, and osteocalcin gene expression in the proximal femur of patients with osteoarthritis with that of patients with femoral neck fracture. Fifty-six patients undergoing arthroplasty because of osteoarthritis or femoral neck fracture were included in the study. Total mRNA was extracted from the bone samples obtained from the intertrochanteric region of the proximal femur. Real-time RT-PCR was used to quantify CTSK (cathepsin K), MMP-9 (matrix metalloproteinase 9), ACP5 (TRAP), TNFSF11 (RANKL), TNFRSF11B (OPG), and BGLAP (osteocalcin) mRNAs. The levels of mRNAs coding for MMP-9 and osteocalcin indicated higher expression in the osteoarthritic group (P = 0.011, P = 0.001, respectively), whereas RANKL expression and the ratio RANKL/OPG were both significantly lower in the osteoarthritic group than in the fracture group. Expression of cathepsin K, MMP-9, and TRAP relative to RANKL was significantly higher in the osteoarthritic group. Ratios of all three proteolytic enzymes relative to formation marker osteocalcin were higher in the fracture group. Gene expression of cathepsin K, MMP-9, TRAP, RANKL, OPG, and osteocalcin and the association between their mRNA levels pointed to higher bone resorption and bone formation in osteoarthritis, differences in balance between them, and differences in regulation of bone resorption in osteoarthritic and osteoporotic bone.

Cellular senescence, ageing and disease

“…MMP activity is normally inhibited by TIMPs (tissue inhibitor of metalloproteinases), but research suggests that that these inhibitors themselves are down-regulated at senescence, thereby further contributing to matrix degradation (Hornebeck 2003). MMP secretion by senescent cells has been suggested to play a role in the progression of disease such as in the pathogenesis of coronary heart disease (CAD) (Nanni et al 2007), and implicated in the progression of osteoporosis, since MMPs play important roles in bone resorption (Logar et al 2007). Price et al (2002) has also shown that the secretion of MMPs by senescent chondrocytes may contribute to the development or progression of osteoarthritis.…”

Analysis of bone matrix composition and trabecular microarchitecture of the femoral metaphysis in patients with osteonecrosis of the femoral head

“…Osteocalcin gene and protein expression is increased in OA bone indicating higher bone resorption and bone formation in OA compared to the healthy situation. 32,33 Therefore, when comparing with bone samples from healthy subjects, an unambiguous increase in osteocalcin deposition in ONFH bone matrix might be detectable. We detected an increased bone volume and bone volume fraction in the femoral canal when assessing trabecular microarchitecture.…”

Tea Polyphenols Inhibit Rat Osteoclast Formation and Differentiation

“…MMPs play a crucial role in tissue remodeling and in the destruction of bone in an arthritic joint due to their ability to degrade a wide variety of extracellular matrix components (26). In particular, MMP-9 is essential with respect to the initiation of the osteoclastic resorption process via removal of the collagenous layer from the bone surface prior to demineralization (27,28). Moreover, MMP-9-knockout mice display only transient disturbances in bone development (27,29).…”

“…In particular, MMP-9 is essential with respect to the initiation of the osteoclastic resorption process via removal of the collagenous layer from the bone surface prior to demineralization (27,28). Moreover, MMP-9-knockout mice display only transient disturbances in bone development (27,29). An in vitro experiment involving calvarial bone revealed that digestion of the bone matrix is inhibited in the presence of an MMP inhibitor (27,30).…”

“…Moreover, MMP-9-knockout mice display only transient disturbances in bone development (27,29). An in vitro experiment involving calvarial bone revealed that digestion of the bone matrix is inhibited in the presence of an MMP inhibitor (27,30). Osteoclasts produce MMPs; furthermore, MMP-9 expression in osteoclasts is markedly higher than in other cell types (31).…”