Stimulation of osteoblast differentiation from mesenchymal stem cells is a potential strategy for bone repair. Bone morphogenetic proteins (BMPs) that induce osteoblastic differentiation have been successfully used in humans to treat fractures. Here we outline a new approach to the stimulation of osteoblast differentiation using small molecules that stimulate BMP activity. We have identified th...

Osteoporosis is a disease characterized by low bone mass, leading to an increased risk of fragility fractures. GATA4 is a zinc-finger transcription factor that is important in several tissues, such as the heart and intestines, and has recently been shown to be a pioneer factor for estrogen receptor alpha (ERα) in osteoblast-like cells. Herein, we demonstrate that GATA4 is necessary for estrogen...

Patients with chronic kidney disease (CKD) on dialysis have 2to 5-fold more coronary artery calcification than age-matched individuals with angiographically proven coronary artery disease. In addition to increased traditional risk factors, CKD patients also have a number of nontraditional cardiovascular risk factors that may play a prominent role in the pathogenesis of arterial calcification, i...

Keratocan is an extracellular matrix protein that belongs to the small leucine-rich proteoglycan family that also includes lumican, biglycan, decorin, mimecan, and fibromodulin. Members of this family are known to play a role in regulating cellular processes such as proliferation and modulation of osteoprogenitor lineage differentiation. The aims of this study were to evaluate the expression pa...

A transient increase in collagen VI expression precedes the accumulation of collagen I associated with interleukin-4 (IL-4)-induced mineralization in human osteoblast-like cells. Transfection with an antisense oligonucleotide specific for alpha1(VI) collagen mRNA was shown to attenuate mRNA levels of collagens VI and I. Incubating IL-4 treated cells with anti-collagen VI antiserum decreased exp...

Cystinosis is recognized as a systemic disease because of mutations in the gene encoding cystinosin, the lysosomal cystine exporter. In the nephropathic form that affects infants and young children, the kidney Fanconi syndrome leads to metabolic acidosis, hypophosphatemia attributable to phosphaturia, and reduced synthesis of the active metabolite of vitamin D, 1,25-dihydroxyvitamin D3, also kn...

BACKGROUND Vascular calcification resembles bone formation and involves vascular smooth muscle cell (SMC) transition to an osteoblast-like phenotype to express Runx2, a master osteoblast transcription factor. One possible mechanism by which Runx2 protein expression is induced is downregulation of inhibitory microRNAs (miR). METHODS AND RESULTS Human coronary artery SMCs (CASMCs) treated with ...

Prostate cancer frequently metastasizes to bone resulting in the formation of osteoblastic metastases through unknown mechanisms. Vascular endothelial growth factor (VEGF) has been shown recently to promote osteoblast activity. Accordingly, we tested if VEGF contributes to the ability of prostate cancer to induce osteoblast activity. PC-3, LNCaP, and C4-2B prostate cancer cell lines expressed b...