Association of Plasma SDF-1 with Bone Mineral Density, Body Composition, and Hip Fractures in Older Adults: The Cardiovascular Health Study

Abstract

Aging is associated with an increase in circulating inflammatory factors. One, the cytokine stromal cell-derived factor 1 (SDF-1 or CXCL12), is critical to stem cell mobilization, migration, and homing as well as to bone marrow stem cell (BMSC), osteoblast, and osteoclast function. SDF-1 has pleiotropic roles in bone formation and BMSC differentiation into osteoblasts/osteocytes, and in osteoprogenitor cell survival. The objective of this study was to examine the association of plasma SDF-1 in participants in the cardiovascular health study (CHS) with bone mineral density (BMD), body composition, and incident hip fractures. In 1536 CHS participants, SDF-1 plasma levels were significantly associated with increasing age (p < 0.01) and male gender (p = 0.04), but not with race (p = 0.63). In multivariable-adjusted models, higher SDF-1 levels were associated with lower total hip BMD (p = 0.02). However, there was no significant association of SDF-1 with hip fractures (p = 0.53). In summary, circulating plasma levels of SDF-1 are associated with increasing age and independently associated with lower total hip BMD in both men and women. These findings suggest that SDF-1 levels are linked to bone homeostasis.

Bone Turnover Status: Classification Model and Clinical Implications

“…Our results are in line with numerous evidences of multidirectional (patho)physiological links between the skeleton as a dynamic, metabolically active organ and the cardiovascular, renal, liver, endocrine, nervous and immune systems. Our observations complement the results from many previous studies showing positive bi- and multi-directional relationships between osteoporosis, falls and fractures, on one hand, and chronic conditions such as CKD 71 , 85 - 90 , CVDs 91 - 104 , anaemia 105 - 111 , hypoalbuminaemia 112 - 114 and hyperthyroidism 115 - 119 on the other, supporting the concept that osteoporosis is a systemic disease.…”

What doesn't kill you makes you stranger: Dipeptidyl peptidase-4 (CD26) proteolysis differentially modulates the activity of many peptide hormones and cytokines generating novel cryptic bioactive ligands

“…Unlike the tightly regulated expression/activity of the transmembrane parent form (CD26) on cells and within tissues, the soluble DPP4 (sCD26) is widely present in plasma and other tissue compartments and is constitutively fully enzymatically active (Klemann, et al, 2016;Mortier, et al, 2016). Indeed endogenous levels of soluble DPP4 may not represent a rate-limiting factor, allowing cleavage of most of its substrate pools in those compartments (Carbone, et al, 2017a;Carbone, et al, 2017b).…”

“…Common sources are tissue stromal/support cells such as mesenchymal derived cells involved in stem cell niche organization, cardiomyocytes, neural stem cells (NSCs), osteogenic cells, and endothelial cells (Carbone, et al, 2017b;Herberg, et al, 2013b;Mortensen & Hill, 2015). For example, we and others have shown that in the brain astrocytes are the primary constitutive source of CXCL12.…”

CoCl2, a mimic of hypoxia, enhances bone marrow mesenchymal stem cells migration and osteogenic differentiation via STAT3 signaling pathway

“…BMSCs are the main source of precursor cells that undergo osteogenic differentiation during fracture healing. The effect of hypoxia on BMSCs homing, proliferation, and differentiation has been widely studied (Carbone et al, ; Wang et al, ). Hypoxia regulates osteogenic cells proliferation and angiogenesis through extracellular regulated protein kinases (ERK)‐1/2 and protein kinase B (AKT) pathway (Nicolaidou et al, ; Guo et al, ).…”