Serum levels of phosphorylated heat shock protein 27 (pHSP27) are associated with bone mineral density in pre- & postmenopausal women: A pilot study

Abstract

Background & objectives:Phosphorylated heat shock protein 27 (pHSP27) has been implicated in the pathogenesis of osteoporosis. Oxidative stress and proinflammatory cytokines, which are known to be involved in aetiology of osteoporosis, can trigger HSP27 phosphorylation. Since pHSP27 is present in circulation, it was hypothesized that serum pHSP27 would be elevated in low bone mineral density (BMD) condition and might serve as an indicator of osteoporosis/osteopenia. Hence, the aim of this study was to examine serum levels of pHSP27 in relation with BMD in pre- and postmenopausal women.Methods:Premenopausal (30 to 40 yr) and postmenopausal (50 to 60 yr) women having either low BMD (osteopenia/osteoporosis) or high BMD were selected (n=80) from a prospective cohort (n=200). Serum levels of pHSP27; along with levels of oestradiol, malondialdehyde, total antioxidant capacity, interleukin (IL)-1, IL-6, tumour necrosis factor - alpha, (TNF-α), c-telopeptide fragments of collagen type I (CTX-1) and osteocalcin were estimated.Results:The serum levels of pHSP27 were significantly elevated in low BMD groups in premenopausal and postmenopausal categories (P<0.05). It also exhibited a significant odds ratio (OR) to differentiate between low and high BMD in both premenopausal (OR=1.734, P=0.013) and postmenopausal (OR=1.463, P=0.042) categories. Additionally, area under the curve to predict low BMD was non-significantly higher for pHSP27 than CTX-1 in premenopausal and postmenopausal categories.Interpretation & conclusions:This study highlights a novel relation between serum pHSP27 and BMD in Indian women however, these findings need to be confirmed in larger studies.

“Omics” Signatures in Peripheral Monocytes from Women with Low BMD Condition

“…We found that heat shock protein 27, also known as heat shock protein beta-1 (HSPB1), was distinctly upregulated in low BMD condition in both premenopausal and postmenopausal categories [ 42 ]. Validation revealed that total HSP27 (tHSP27) and phosphorylated HSP27 (pHSP27) were elevated in low BMD condition in both categories not only in monocytes but also in sera [ 42 , 43 ]. Interestingly, pHSP27 exhibited a higher odds ratio than tHSP27 to predict low BMD, irrespective of menopausal status [ 43 ].…”

“…Validation revealed that total HSP27 (tHSP27) and phosphorylated HSP27 (pHSP27) were elevated in low BMD condition in both categories not only in monocytes but also in sera [ 42 , 43 ]. Interestingly, pHSP27 exhibited a higher odds ratio than tHSP27 to predict low BMD, irrespective of menopausal status [ 43 ]. Performance characteristics exhibited by pHSP27 and collagen type 1 cross-linked C-telopeptide (CTX-1) were comparable; however, pHSP27 showed lower sensitivity than CTX-1 and lower or comparable specificity than CTX-1 [ 43 ].…”

“…Interestingly, pHSP27 exhibited a higher odds ratio than tHSP27 to predict low BMD, irrespective of menopausal status [ 43 ]. Performance characteristics exhibited by pHSP27 and collagen type 1 cross-linked C-telopeptide (CTX-1) were comparable; however, pHSP27 showed lower sensitivity than CTX-1 and lower or comparable specificity than CTX-1 [ 43 ]. Besides its well-known antiapoptotic properties, phosphorylated HSP27 increased monocyte migration towards both MCP-1 and RANKL [ 42 ].…”