Disease relevance of Osteolysis

• Impaired intranuclear trafficking of Runx2 (AML3/CBFA1) transcription factors in breast cancer cells inhibits osteolysis in vivo [1].
• Anti-alpha4 integrin antibody suppresses the development of multiple myeloma and associated osteoclastic osteolysis [2].
• Using a quantitative in vivo model of wear debris-induced osteolysis, we show that Etanercept prevents bone resorption and osteoclastogenesis [3].
• Studies on myeloma bone disease showed the ligand for receptor activator of nuclear transcription factor-kappaB (RANKL) was expressed on tumor cells and stromal cells associated with myeloma cells and was critical for osteoclast-induced osteolysis [4].
• Increased local osteoclast (OC)-mediated bone resorption coincides with angiogenesis in normal bone development and fracture repair, as well as in pathological disorders such as tumor-associated osteolysis and inflammatory-related rheumatoid arthritis or periodontal disease [5].

High impact information on Osteolysis

• Mutations in TNFRSF11A, affecting the signal peptide of RANK, cause familial expansile osteolysis [6].
• Familial expansile osteolysis (FEO, MIM 174810) is a rare, autosomal dominant bone disorder characterized by focal areas of increased bone remodelling [6].
• TNF-alpha is the dominant cytokine in inflammatory osteolysis [7].
• M-CSF mediates TNF-induced inflammatory osteolysis [7].
• These data suggest that TNF regulates RANKL expression via IL-1, and, therefore, IL-1 plays a role in TNF-induced periarticular osteolysis [8].

Chemical compound and disease context of Osteolysis

• PURPOSE: Despite evidence that clodronate inhibits tumor-induced osteolysis, no studies have directly assessed the optimal dose for long-term treatment [9].
• The parenteral administration of three diphosphonates, dichloromethylene diphosphonate, ethanehydroxydiphosphonate , and aminopropanediphosphonate , at 16 and 160 mumol/kg/day, protects the bones by decreasing the extent of osteolysis [10].
• Low-dose gallium nitrate for prevention of osteolysis in myeloma: results of a pilot randomized study [11].
• Thus, HSP90 inhibitors can stimulate osteoclast formation, which may underlie the increased incidence of osteolysis and skeletal tumor incidence caused by 17-AAG in vivo [12].
• It is concluded that in metaphyseal bone 1,25-(OH)2D3 increased the number and synthetic activity of osteoblasts without significantly enhancing osteoclasis or osteocytic osteolysis [13].

Biological context of Osteolysis

• Thus, in addition to enhanced osteolysis, MM cells also suppress bone formation at least in part through an inhibition of the canonical Wnt pathway by secreting sFRP-2 [14].
• Here we examined the effects of a monoclonal antibody to alpha4 integrin (anti-alpha4 Ab) that disrupts myeloma cell-stromal cell interactions mediated via alpha4beta1 integrin and vascular cell adhesion molecule-1 (VCAM-1) on myeloma cell growth in bone marrow and accompanying osteolysis [2].
• Mice injected with cells overexpressing PTHrP and OPG showed enhanced tumor growth, increased osteolysis (2-fold compared with MCF-7 cells overexpressing PTHrP), and altered histology that was reflective of a less differentiated (more aggressive) phenotype compared with MCF-7 cells [15].
• In this study, we investigated the effect of parthenolide (PAR) on LPS-induced osteolysis in vivo and studied its role in osteoclastogenesis, bone resorption, apoptosis, and NF-kappaB activity [16].
• This tapered titanium femoral component appears to provide excellent short-term stability, without resorptive bone-remodeling, osteolysis, or a high prevalence of pain in the thigh [17].

Anatomical context of Osteolysis

• Thus, osteolysis attending relatively modest elevations in ambient TNF-alpha depends upon responsive stromal cells [18].
• To explore a possible role of cathepsin L in osteolysis, GCT-derived, cathepsin L-expressing, mononuclear cells were cultured on dentine disks [19].
• Periprosthetic osteolysis: induction of vascular endothelial growth factor from human monocyte/macrophages by orthopaedic biomaterial particles [20].
• Stress-induced osteolysis of the clavicle [21].
• Prelymphomatous B cell hyperplasia in the bone marrow of interleukin-7 transgenic mice: precursor B cell dynamics, microenvironmental organization and osteolysis [22].

Gene context of Osteolysis

• Here, we show that proper Runx2 subnuclear targeting is required for osteolysis [1].
• PTHrP induces local osteolysis that leads to activation of bone matrix-borne transforming growth factor beta (TGF beta) [23].
• We evaluated protease expression and cellular distribution of the proteolytic machinery responsible for the osteolysis. mRNA profiles showed that cathepsin K, cathepsin L, and matrix metalloproteinase (MMP)-9 were the preferentially expressed collagenases [19].
• Thus, targeting TNF and/or its p55 receptor may arrest wear particle osteolysis [24].
• More importantly, blockade of NEMO assembly with the IKK complex is a viable strategy to avert inflammatory osteolysis [25].
• An uncommon haplotype within the promoter region of the gene for IL-6 is positively associated with osteolysis [26].

Analytical, diagnostic and therapeutic context of Osteolysis

• Variation in the TNF gene promoter and risk of osteolysis after total hip arthroplasty [27].
• No bone osteolysis could be discovered in any of the patients a few weeks after mastectomy operation, but PGE2 analysis of breast tumors may have prognostic value for the future [28].
• This is the first evidence that in vivo OPG gene therapy can be used to prevent wear debris-induced osteolysis [29].
• In the initially well-fixed hydroxyapatite-coated prostheses the sealing effect of a hydroxyapatite coating creates high concentrations of polyethylene in the limited joint space, resulting in massive proximal femoral osteolysis [30].
• Tissue retrieved from failed total hip replacements often has large quantities of particulate PE and most particles associated with peri-implant osteolysis are oxidised [31].

References