cholecalciferol and Osteoarthritis

Biomarkers are essential tools in osteoarthritis (OA) research, clinical trials, and drug development. Detecting and evaluating biomarkers in OA research can open new avenues for researching and developing new therapeutics. In the present report, we have explored the serological detection of various osteoarthritis-related biomarkers in the preclinical model of OA. In this surgical OA model, we disrupted the medial tibial cartilage's integrity via anterior cruciate ligament transection combined with medial meniscectomy (ACLT+MMx) of a single joint of Wistar rats. The progression of OA was verified, as shown by the microscopic deterioration of cartilage and the increasing cartilage degeneration scoring from 4 to 12 weeks postsurgery. The concentration of serological biomarkers was measured at two timepoints, along with the complete blood count and bone electrolytes, with biochemical analysis further conducted. The panel evaluated inflammatory biomarkers, bone/cartilage biomarkers, and lipid metabolic pathway biomarkers. In chronic OA rats, we found a significant reduction of total vitamin D3 and C-telopeptide fragments of type II (CTX-II) levels in the serum as compared to sham-operated rats. In contrast, the serological levels of adiponectin, leptin, and matrix metallopeptidase (MMP3) were significantly enhanced in chronic OA rats. The inflammatory markers, blood cell composition, and biochemical profile remained unchanged after surgery. In conclusion, we found that a preclinical model of single-joint OA with significant deterioration of the cartilage can lead to serological changes to the cartilage and metabolic-related biomarkers without alteration of the systemic blood and biochemical profile. Thus, this biomarker profile provides a new tool for diagnostic/therapeutic assessment in OA scientific research.

Topics: Adiponectin; Animals; Anterior Cruciate Ligament; Anterior Cruciate Ligament Injuries; Biomarkers; Cartilage, Articular; Cholecalciferol; Collagen Type II; Disease Models, Animal; Leptin; Matrix Metalloproteinase 3; Meniscectomy; Menisci, Tibial; Osteoarthritis; Peptide Fragments; Rats; Rats, Wistar; Tibia

Osteoarthritis (OA) is the most common type of arthritis and proinflammatory cytokines have been considered as the main etiologic factor in the pathogenesis of the disease. Serum levels of cytokines, that are associated with innate immunity and TH1 cells, have been analyzed in OA patients, however, there is limited research that profiles cytokines associated with Th17 cells and their relation to vitamin D3 and pain.. The sera from 131 patients with OA and 262 healthy controls were evaluated for serum levels of IL-17A, IL-21, IL-23 and vitamin D3 using ELISA.. Serum levels of IL-17A, and IL-23 were statistically higher in OA patients than in healthy controls, while IL-21 and vitamin D3 were significantly lower in OA patients when compared to controls. A significant positive correlation was found between the serum levels of IL-17A and IL-23 using WOMAC pain scores and vitamin D3 serum levels.. The results suggest that IL-17A plays a significant role in OA pathogenesis and the induction of pain. Decreased serum levels of vitamin D3 may reflect a positive role played by the factor in the regulation of immune responses in OA patients.

Topics: Adult; Case-Control Studies; Cholecalciferol; Cross-Sectional Studies; Female; Humans; Interleukin-17; Interleukin-23; Interleukins; Male; Osteoarthritis; Pain

The paper considers the current pathogenesis, by choosing the actual targets of pharmacotherapy with available drugs. It reflects the cytokine mechanisms responsible for lesion of the synovial membranes, cartilage, and subchondral bone. Particular emphasis is laid on the role of chondroitin sulfate, glucosamine, vitamin D3 as drugs that affect the key components of pathogenesis, including the volume of resorptive cavities in the subchondral bone.

Topics: Bone Density; Bone Density Conservation Agents; Bone Resorption; Cholecalciferol; Chondroitin Sulfates; Cytokines; Glucosamine; Humans; Osteoarthritis; Treatment Outcome

To evaluate the expression of Dickkopf-1 protein factor (DKK-1), DKK-2, and β-catenin, components of the Wnt pathway, in human osteoarthritic (OA) and osteoporotic (OP) osteoblasts and to correlate it to cell metabolic activity, proliferation, and receptor activator of nuclear factor-κB ligand/osteoprotegerin (RANKL/OPG) expression.. Primary human osteoblast cultures were obtained from healthy, OA, and OP donors. In each cell population we evaluated DKK-1, DKK-2, nonphosphorylated β-catenin and RANKL/OPG expression, osteocalcin and alkaline phosphatase (ALP) synthesis, and cell proliferation, both in basal condition and after vitamin D3 stimulation.. DKK-1 and DKK-2 showed opposite patterns of expression in OA and OP osteoblasts. The RANKL/OPG ratio was significantly higher in the OP group because of a greater expression of RANKL, whereas it was significantly lower in the OA group because of a higher expression of OPG. Treatment with vitamin D3 increased the RANKL/OPG ratio and DKK-2 expression and reduced DKK-1 expression in each cell population, but did not affect β-catenin levels. Both osteocalcin and ALP production and cell proliferation were enhanced in OA cells and reduced in the OP ones.. These data confirm that OA and OP are characterized by opposite bone changes, consisting of reduced bone remodeling processes with increased osteoblast activity in OA, and enhanced bone resorptive activity with reduction of osteoblast metabolism in OP, and suggest that the Wnt pathway is involved in the pathogenesis of both diseases.

Topics: Adult; Aged; Alkaline Phosphatase; Bone Resorption; Cell Proliferation; Cells, Cultured; Cholecalciferol; Female; Humans; Intercellular Signaling Peptides and Proteins; Male; Middle Aged; Osteoarthritis; Osteoblasts; Osteoporosis; Osteoprotegerin; RANK Ligand; Wnt Signaling Pathway

Vascular Endothelial Growth Factor (VEGF) is a potent angiogenic factor, which also regulates bone remodeling. Osteoblasts not only respond to VEGF stimulation, but also express and synthesize this factor. The present study was aimed to evaluate in vitro differences in VEGF production and expression of cultured human osteoblastic cells derived from healthy donors and from subjects affected by osteoarthritis and osteoporosis, under basal conditions than after vitamin D3, and to investigate the angiogenic activity of culture media obtained by these cells in chick embryo chorioallantoic membrane (CAM) assay. The results showed that normal and pathological osteoblasts produce and express VEGF and 1,25 dihydroxy-vitamin D3 treatment increases protein and m-RNA VEGF levels. In addition culture media of pathological osteoblasts induce a strong angiogenic response, greater than observed with culture medium of normal cells, suggesting the involvement of osteoblast-derived VEGF in the pathogenesis of bone diseases.

Topics: Adult; Aged; Animals; Bone Density Conservation Agents; Cells, Cultured; Chick Embryo; Cholecalciferol; Chorioallantoic Membrane; Culture Media; Female; Humans; Male; Middle Aged; Neovascularization, Physiologic; Osteoarthritis; Osteoblasts; Osteoporosis; Vascular Endothelial Growth Factor A; Vitamins

To evaluate vascular endothelial growth factor (VEGF) mRNA expression and protein synthesis in primary human osteoblast cultures from healthy, osteoporotic and osteoarthritic subjects. Normal primary human osteoblast cultures were obtained from healthy subjects undergoing surgery for the reduction in traumatic fractures. Pathological osteoblasts were obtained from patients undergoing to total hip replacement for osteoporotic hip fracture or advanced osteoarthritis. VEGF mRNA expression and protein synthesis were evaluated in cultured cells, by semiquantitative real-time PCR and ELISA, respectively, both under basal conditions than after vitamin D3 stimulation. Osteoarthritic osteoblasts showed a significantly higher VEGF expression compared to the normal and OP osteoblasts, both under basal conditions than in the presence of vitamin D3, whereas no difference was found between osteoporotic and normal osteoblast. Vitamin D3 significantly enhanced VEGF expression in normal and pathological osteoblasts. This preliminary study supports the hypothesis that VEGF is involved in the pathogenic mechanisms underlying the bone alterations typical of osteoarthritis and confirms the crucial role of vitamin D3 supplementation in metabolic bone diseases.

Topics: Adult; Aged; Cells, Cultured; Cholecalciferol; Enzyme-Linked Immunosorbent Assay; Gene Expression Profiling; Humans; Middle Aged; Osteoarthritis; Osteoblasts; Osteoporosis; Real-Time Polymerase Chain Reaction; Vascular Endothelial Growth Factor A

To compare 3 different cholecalciferol supplementation regimens in patients with rheumatic diseases.. One hundred fifty-four patients who completed a 6-month course of cholecalciferol supplementation, of whom 111 had an autoimmune/inflammatory rheumatic disease (ARD) and 43 osteoarthritis (NARD), were retrospectively identified from a database of 872 consecutive adult patients who attended a tertiary level immuno-rheumatology clinic from 2007 to 2010. Patients with renal failure or primary hyperparathyroidism were excluded. Plasma 25-hydroxy vitamin D [25(OH)D] and parathyroid hormone (PTH) concentrations were evaluated at baseline and after completion of treatment with (i) a single oral dose of cholecalciferol 300,000 IU, followed by oral cholecalciferol 800-1000 IU daily for 6 months [high-dose loading treatment (HLT) group; n = 40]; (ii) a single oral dose of cholecalciferol 100,000 IU, followed by daily oral cholecalciferol as above [low-dose loading treatment (LLT) group; n = 30]; or (iii) daily oral cholecalciferol as above but without the loading dose [standard therapy (ST); n = 84].. The rates of serum 25(OH)D and PTH normalization (defined as values > 75 nmol/l and < 72.9 pg/ml, respectively) were as follows: HLT, 52.5% (95% CI 37.5-68.5) and 69.2% (95% CI 54.7-83.3); LLT, 36.7% (95% CI 19.7-54.3) and 53.8% (95% CI 36.2-71.8); ST, 31.0% (95% CI 21.1-40.9) and 35.0% (95% CI 14.1-55.9). All regimes increased 25(OH)D (p < 0.001) but only HLT reduced PTH (p < 0.01) in comparison to baseline. The ARD group had a similar 25(OH)D increase but a smaller PTH reduction than the NARD (p < 0.05).. An HLT cholecalciferol regimen is needed to correct hypovitaminosis D of patients with rheumatic diseases, with superior 25(OH)D normalization and PTH suppression rates at 6 months.

Topics: Aged; Autoimmune Diseases; Bone Density Conservation Agents; Cholecalciferol; Dose-Response Relationship, Drug; Female; Humans; Male; Medical Records; Middle Aged; Osteoarthritis; Parathyroid Hormone; Retrospective Studies; Rheumatic Diseases; Vitamin D; Vitamin D Deficiency

The objective of this study was to evaluate the metabolic in vitro effect of the bisphosphonate neridronate on normal and pathological human osteoblasts. Primary human osteoblast cultures were obtained from cancellous bone of osteoarthritic (OA) and osteoporotic (OP) patients and a corresponding healthy control group. Osteocalcin production was evaluated by cultured cells in neridronate 10(-4) M and 10(-6) M, both under basal conditions and after vitamin D3 stimulation. In the absence of neridronate, vitamin D3 increased osteocalcin production in all cell cultures; under the same conditions, and in the absence of vitamin D3, OA osteoblasts showed a significantly higher osteocalcin production whereas OP osteoblasts showed a significantly lower osteocalcin production compared to the normal osteoblasts, respectively. In all cellular populations neridronate at a higher concentration (10(-4) M) induced a reduction in osteocalcin synthesis, but in normal and osteoarthritic osteoblasts did not reduce the stimulatory effect of vitamin D3, whereas it inhibited the vitamin D3-induced increase of osteocalcin synthesis in the osteoporotic cells. In normal and osteoporotic osteoblasts stimulation with the lower neridronate concentration (10(-6) M) significantly increased osteocalcin production, which was further enhanced by vitamin D3 as an additional effect of the combined treatment. In OA osteoblasts, neridronate 10(-6) M did not induce an increase in osteocalcin synthesis and the additional effect of combined treatment with vitamin D3 was not observed. Neridronate can modify the metabolic activity of human osteoblasts by enhancing or decreasing their biosynthetic activity, both in normal and in pathological conditions, depending on compound concentration and on different cell types. These results confirm the validity of using neridronate at doses usually administered in treating osteoporosis, and they suggest using it to treat other diseases which show an altered osteoblast metabolism, such as osteoarthritis.

Topics: Adult; Aged; Cells, Cultured; Cholecalciferol; Diphosphonates; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged; Osteoarthritis; Osteoblasts; Osteocalcin; Osteoporosis

1,25-dihydroxyvitamin D3 (1,25(OH)2 D3) has been shown to modulate lymphocyte activation in vitro. Through binding to specific receptors 1,25-(OH)2 D3 inhibits proliferation, immunoglobulin production and the release of cytokines. Moreover, 1,25-(OH)2 D3 is efficiently produced by activated monocytes. These findings suggest that 1,25-(OH)2 D3 may play a role as a regulator of immunological activation. Consequently, we found it of interest to study the serum levels of the two major metabolites of vitamin D3 in patients with systemic lupus erythematosus (SLE) (n = 21), rheumatoid arthritis (RA) (n = 29) and osteoarthritis (n = 12). In patients with SLE the levels of 25-OH D3 were below those of the healthy controls (p = 0.0008) and OA (p = 0.0168). The levels 1,25-(OH)2 D3 corresponded to normal levels. There were no significant correlations between 25-OH D3 levels and clinical or paraclinical disease manifestations. Further, the phenotypic distribution of Gc-globulin, which binds vitamin D3 metabolites in circulation, was normal. The serum concentrations of 1,25-(OH)2 D3 and 25-OH D3 in patients with RA and OA corresponded to those of the controls. Although the cause of the reduced 25-OH D3 levels in SLE patients is unclear, possible beneficial effects of administration of vitamin D to these patients should be considered.

Topics: Adult; Aged; Antirheumatic Agents; Arthritis, Rheumatoid; Calcifediol; Calcitriol; Cholecalciferol; Female; Humans; Lupus Erythematosus, Systemic; Male; Middle Aged; Osteoarthritis; Vitamin D-Binding Protein

Cellular mechanisms accounting for the osteolysis of rheumatoid erosions are poorly understood. Cells were isolated and characterised from the synovium of 16 patients with rheumatoid arthritis (RA) and four patients with osteoarthritis and their ability to resorb bone was assessed using a scanning electron microscope bone resorption assay. Macrophages were the major cell type isolated from the synovium of patients with RA. These produced extensive roughening of the bone surface without resorption pit formation. This low grade type of bone resorption was not affected by systemic (calcitonin, parathyroid hormone, 1,25-dihydroxyvitamin D3) or local (interleukin 1, prostaglandin E2) factors influencing bone resorption. Macrophage mediated bone resorption differs qualitatively and quantitatively from that of osteoclasts but is likely to play an important part in the development of marginal erosions in RA.

Topics: Adult; Aged; Arthritis, Rheumatoid; Bone and Bones; Bone Resorption; Calcitonin; Cells, Cultured; Cholecalciferol; Female; Humans; Interleukin-1; Macrophages; Male; Microscopy, Electron, Scanning; Middle Aged; Osteoarthritis; Parathyroid Hormone; Prostaglandins; Rheumatic Diseases; Synovial Membrane