Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0151825 (bone pain)
 3,118 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bone manifestations are frequent in Gaucher disease (GD), the most prevalent lysosomal storage disorder. Currently, therapy with enzyme replacement (ERT) or substrate reduction (SRT) is available. We investigated changes of laboratory parameters associated with bone metabolism in GD patients switching from ERT to SRT. Seven GD patients consecutively treated with ERT and SRT were studied. All patients had different degrees of bone involvement. Laboratory results were acquired at the time of change from ERT to SRT (0 months) and while on SRT (6 months, 12-18 months). Markers of GD activity remained stable or showed statistically insignificant increases. Six patients had stable skeletal manifestations and reported no bone-associated symptoms. One patient presented progressive bone manifestations on magnetic resonance imaging and experienced increasing bone pain. Osteocalcin, alkaline phosphatase, and C-terminal telopeptide of collagen I were initially within the lower part of the normal range and decreased during SRT (alkaline phosphatase P = 0.0169, osteocalcin nonsignificant, C-terminal telopeptide of collagen I nonsignificant). Tartrate-resistant acid phosphatase 5b was initially normal or slightly increased, and macrophage colony-stimulating factor was within the normal lower range; both parameters remained stable. Interleukin-6 was elevated only in the patient with progressive bone disease. Macrophage inflammatory protein 1alpha (MIP-1alpha) was elevated without change after switching to SRT. MIP-1beta was within the normal range, and no values were above 85 ng/mL, indicative of active skeletal disease. From a clinical and metabolic point of view, most skeletal manifestations and bone-associated laboratory parameters remain stable after switch from ERT to SRT.
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PMID:Changes of bone metabolism in seven patients with Gaucher disease treated consecutively with imiglucerase and miglustat. 1855 43

Bone disease is the most frequent complication in multiple myeloma (MM) resulting in osteolytic lesions, bone pain, hypercalcemia and renal failure. In MM bone disease the perfect balance between bone-resorbing osteoclasts (OCs) and bone-forming osteoblasts (OBs) activity is lost in favour of OCs, thus resulting in skeletal disorders. Since exosomes have been described for their functional role in cancer progression, we here investigate whether MM cell-derived exosomes may be involved in OCs differentiation. We show that MM cells produce exosomes which are actively internalized by Raw264.7 cell line, a cellular model of osteoclast formation. MM cell-derived exosomes positively modulate pre-osteoclast migration, through the increasing of CXCR4 expression and trigger a survival pathway. MM cell-derived exosomes play a significant pro-differentiative role in murine Raw264.7 cells and human primary osteoclasts, inducing the expression of osteoclast markers such as Cathepsin K (CTSK), Matrix Metalloproteinases 9 (MMP9) and Tartrate-resistant Acid Phosphatase (TRAP). Pre-osteoclast treated with MM cell-derived exosomes differentiate in multinuclear OCs able to excavate authentic resorption lacunae. Similar results were obtained with exosomes derived from MM patient's sera. Our data indicate that MM-exosomes modulate OCs function and differentiation. Further studies are needed to identify the OCs activating factors transported by MM cell-derived exosomes.
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PMID:Involvement of multiple myeloma cell-derived exosomes in osteoclast differentiation. 2594 96