The effect of glucocorticoids on Thrombospondin‐1, Osteocalcin and the Thrombospondin‐1:Osteocalcin ratio in humans

Abstract

Objective: Thrombospondin-1 (TSP1), a matricellular protein, and Osteocalcin (OCN), a noncollagenous protein secreted by osteoblasts, are known to be up-and downregulated, respectively, by glucocorticoids. The aim of this study was to determine whether a ratio between TSP1:OCN was altered by changes in glucocorticoid activity in humans. Design: Prospective observational study.Setting: Tertiary university hospital in Queensland, Australia. Patients and Measurements:Patients with Cushing's syndrome (CS, n = 19), asthma or giant cell arteritis on chronic prednisolone treatment (PRED, n = 13), adrenal insufficiency (AI, n = 16) and healthy volunteers (HV, n = 20). Plasma TSP1 and serum total OCN were measured by immunoassay at 0800h, 1200h and 1600h in patients with CS, patients with AI taking replacement glucocorticoids, HV before and after 4 mg dexamethasone and PRED patients predose at 800 and 4 hours post-dose at 1200 hours.Results: Plasma TSP1 in CS was higher (P < .0001), and serum OCN was lower (P < .0001) than HV. The TSP1:OCN ratio in HV increased significantly after 4 mg dexamethasone (P < .0001) and in AI after taking their hydrocortisone replacement therapy (P < .001). PRED patients had a higher TSP1:OCN ratio compared with HV at both 800 and 1200 hours (both P < .001), but no significant change occurred from pre-to post-dose. A TSP1:OCN ratio of >73 at 800 hours differentiated CS from HV with a sensitivity of 95% and a specificity of 100%. Conclusions:The TSP1:OCN ratio is elevated in patients on prednisolone and in patients with CS compared with healthy volunteers. It may be a useful biomarker of total body glucocorticoid activity in humans. K E Y W O R D Sadrenal insufficiency, biomarker, Cushing's syndrome, glucocorticoid | 729 CESANA-NIGRO Et Al.

Serum proteome profiles in cats with chronic enteropathies

“…Additional cohort studies between cats with LGAL and CE, food responsive and immunosuppressant responsive enteropathies are warranted. THBS1 is a glucocorticoid responsive protein in humans and was elevated in human patients being treated with prednisolone and with Cushing's syndrome 41,42 . In our study, no correlation was found between THBS1 abundance and cats treated with prednisolone in all groups.…”

Ex vivo glucocorticoid‐induced secreted proteome approach for discovery of glucocorticoid‐responsive proteins in human serum

“…These new glucocorticoid response serum protein biomarkers warrant further validation in additional clinical cohorts. While the glucocorticoid‐responsive proteins we have identified are unlikely to change in concentration solely in response to alterations in glucocorticoid activity, by combining biomarkers in a panel, the specificity is likely to increase, as we have previously shown in applying a ratio between thrombospondin‐1 and osteocalcin [6].…”

“…Both pre-and post-DEX blood samples were drawn at 1200 h to eliminate diurnal changes in concentration as a cause for any observed differences. As we previously introduced the concept of a ratio between an upand down-regulated serum proteins [6], we also investigated ratios between HMGB2 and LYZ. Encouragingly, we found that the ratio between HMGB2 and LYZ increased in 90% of participants following DEX (from 8.4 ± 0.45 to 15.7 ± 1.14, p < 0.0001), showing potential utility as a clinical indicator of DEX responsiveness.…”

“…Our group recently reported that a ratio of an upregulated protein, thrombospondin‐1, to a down regulated protein, osteocalcin can indeed reflect the total body glucocorticoid activity in humans with endogenous and exogenous glucocorticoid excess [6]. The aim of this study was to explore the possibility of additional circulating glucocorticoid responsive proteins being measurable in humans.…”

Osteoporosis in Patients With Respiratory Diseases

“…As for corticosteroid-induced bone loss, some prospective observational studies revealed that long-term oral corticosteroids decreased the mineralization of bone tissue ( Park et al, 2015 ). Osteocalcin was usually lowered with corticosteroid intake ( Puolijoki et al, 1992 ; Cesana‐Nigro et al, 2019 ), and biosynthesis of Collagen I was also interfered by corticosteroids ( Puolijoki et al, 1996 ). These significantly decreasing osteogenic markers also reflected the weakness of osteoblasts with corticosteroid treatment ( Brabnikova Maresova et al, 2013 ).…”