Regulation of bone matrix protein expression and induction of differentiation of human osteoblasts and human bone marrow stromal cells by bone morphogenetic protein-2

Lecanda, Fernando; Avioli, Louis V.; Cheng, Su‐Li

doi:10.1002/(sici)1097-4644(19971201)67:3<386::aid-jcb10>3.0.co;2-b

Cited by 246 publications

(135 citation statements)

References 55 publications

Supporting

Mentioning

118

Contrasting

Unclassified

Order By: Relevance

“…For valvular calcification studies, digital photomicrographs were captured with a Spot Enhanced camera mounted on a Zeiss Axiovert S100 microscope. Mineral deposition was visualized with Alizarin red (calcium) (29) or von Kossa (phosphate) (15) stains, and the mineralized leaflet area was quantified using Kodak one-dimensional automated image analysis software version 3.5.3. The data are expressed as the percentage of mineralized area of total valve leaflet area (pixel counts) from digital photomicrograph images, averaging results over five adjacent 5-micron sections for each animal (n ϭ 5-6 animals/treatment arm).…”

Section: Methodsmentioning

confidence: 99%

Teriparatide (Human Parathyroid Hormone (1–34)) Inhibits Osteogenic Vascular Calcification in Diabetic Low Density Lipoprotein Receptor-deficient Mice

Shao

Cheng

Charlton-Kachigian

et al. 2003

Journal of Biological Chemistry

Self Cite

166

149

View full text Add to dashboard Cite

Over a century ago, the pathologist Rudolph Virchow recognized the involvement of calcified tissues in the pathobiology of vascular diseases (1). Coining the term "endarteritis deformans" he descriptively denoted the histological character of the atherosclerotic plaque as exhibiting features of a progressively calcified scar tissue that forms in response to a vascular inflammatory state. Since then, a minimum of three histoanatomic variants of macrovascular calcification, atherosclerosis, calcific valvular sclerosis, and medial artery calcification, have been shown arise in response to metabolic, mechanical, infectious, or inflammatory diseases (2-4). Both early and recent studies point to cellular processes that resemble bone formation at the histological level. However, Demer and co-workers (5) were the first to provide direct evidence for active osteogenic regulation of vascular calcification. They identified BMP2, 1 a powerful bone morphogenetic protein, as a key component of the mineralized atherosclerotic plaque (5). Thus, rather than being a passive process, vascular calcification is in part subject to active regulation. Once thought benign, the deleterious clinical consequences of calcific vasculopathy are now becoming clearer (6 -10). Patients with diabetes have increased mortality and 3-fold increased risk for lower extremity amputation in the setting of medial artery calcification (11). In patients with asymptomatic aortic stenosis, a moderate to severe echocardiographic valve calcification score is the single best predictor of vascular disease progression, again exceeding blood pressure control, lipid control, and diabetes control in positive predictive value (12). Risk for stroke, particularly notable in post-menopausal women, is increased in the presence of aortic arch calcification (13). Multiple metabolic stimuli contribute to calcific vascular disease initiation and progression in patients with diabetes, hypercholesterolemia, poor glycemic control, and phosphate retention associated with renal failure contributing to vascular calcium accumulation (2). A fundamental understanding the molecular physiology of vascular calcification will provide insights useful for developing strategies to prevent and treat this macrovascular disease process.Metabolic contributions to vascular calcification are well known and include hypercholesterolemia, diabetes, hyperphosphatemia, vitamin D toxicosis, magnesium deficiency, and chronic renal insufficiency (2). The mechanisms whereby the metabolic insults of diabetes initiate and propagate vascular calcification are beginning to be examined in detail. Hyperglycemia, hyperlipidemia, and oxidative stress (3, 14) up-regulate the expression of vascular signaling molecules that promote mineral deposition in a process that resembles craniofacial bone formation (15). Hyperglycemia and hyperlipidemia have

show abstract

Section: Methodsmentioning

confidence: 99%

Teriparatide (Human Parathyroid Hormone (1–34)) Inhibits Osteogenic Vascular Calcification in Diabetic Low Density Lipoprotein Receptor-deficient Mice

Shao

Cheng

Charlton-Kachigian

et al. 2003

Journal of Biological Chemistry

Self Cite

166

149

View full text Add to dashboard Cite

show abstract

“…Human aortic smooth muscle cell cultures isolated from atherosclerotic aortas demonstrated a BMP-2-and -4 -activated osteoblastic gene transcription program. 23 Phosphorus stimulated mineralization of the extracellular matrix (ECM) of these cultures analogous to bone formation in vitro. Mineralization was blocked by a BMP antagonist, noggin, in the presence of high phosphorus.…”

mentioning

confidence: 99%

The Mechanism of Phosphorus as a Cardiovascular Risk Factor in CKD

Mathew¹,

Tustison²,

Sugatani³

et al. 2008

Journal of the American Society of Nephrology

210

171

View full text Add to dashboard Cite

Hyperphosphatemia and vascular calcification have emerged as cardiovascular risk factors among those with chronic kidney disease. This study examined the mechanism by which phosphorous stimulates vascular calcification, as well as how controlling hyperphosphatemia affects established calcification. In primary cultures of vascular smooth muscle cells derived from atherosclerotic human aortas, activation of osteoblastic events, including increased expression of bone morphogenetic protein 2 (BMP-2) and the transcription factor RUNX2, which normally play roles in skeletal morphogenesis, was observed. These changes, however, did not lead to matrix mineralization until the phosphorus concentration of the media was increased; phosphorus stimulated expression of osterix, a second critical osteoblast transcription factor. Knockdown of osterix with small interference RNA (siRNA) or antagonism of BMP-2 with noggin prevented matrix mineralization in vitro. Similarly, vascular BMP-2 and RUNX2 were upregulated in atherosclerotic mice, but significant mineralization occurred only after the induction of renal dysfunction, which led to hyperphosphatemia and increased aortic expression of osterix. Administration of oral phosphate binders or intraperitoneal BMP-7 decreased expression of osterix and aortic mineralization. It is concluded that, in chronic kidney disease, hyperphosphatemia stimulates an osteoblastic transcriptional program in the vasculature, which is mediated by osterix activation in cells of the vascular tunica media and neointima. Chronic kidney disease (CKD) is a fatal illness, and cardiovascular complications are the major causes of morbidity and mortality. 1,2 The causes of the excess cardiovascular mortality associated with CKD are unknown, because the role of the standard risk factors associated with cardiovascular mortality do not account for the increased risk in CKD. 2 There is strong epidemiologic evidence that serum phosphorus is an independent risk factor for cardiovascular events and mortality in CKD. 3,4 The serum phosphorus has been linked to another cardiovascular risk factor, vascular calcification (VC), 3,5,6 an important cause of vascular stiffness in CKD leading to increased pulse wave velocity, increased cardiac work, left ventricular hypertrophy, and decreased coronary artery blood flow. 6 -8 Phosphorus has been further implicated as a cause of VC through studies in vitro that have demonstrated that it induces phenotypic changes in vascular smooth muscle cells (VSMC) by increasing gene transcription of proteins involved in osteoblast function-bone formation 9 and stimulating matrix mineralization. 10 -12 In the uremic calcifying environment, expression of the contractile proteins of VSMC, such as ␣-smooth muscle actin, SM22,

show abstract

“…TGFβ 1 (25 kDa) influences the proliferation and differentiation of the stem cells (28), while BMP 2 (26 kDa) stimulates the production of specific bone matrix proteins (29,30). The proteins were embedded within a film of alternating layers of the polypeptides poly-L-lysine (PLL) and poly-L-glutamic acid (PGA) (31,32).…”

mentioning

confidence: 99%

Active multilayered capsules for in vivo bone formation

Facca

Cortez

Mendoza-Palomares

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

118

View full text Add to dashboard Cite

Interest in the development of new sources of transplantable materials for the treatment of injury or disease has led to the convergence of tissue engineering with stem cell technology. Bone and joint disorders are expected to benefit from this new technology because of the low self-regenerating capacity of bone matrix secreting cells. Herein, the differentiation of stem cells to bone cells using active multilayered capsules is presented. The capsules are composed of poly-L-glutamic acid and poly-L-lysine with active growth factors embedded into the multilayered film. The bone induction from these active capsules incubated with embryonic stem cells was demonstrated in vitro. Herein, we report the unique demonstration of a multilayered capsule-based delivery system for inducing bone formation in vivo. This strategy is an alternative approach for in vivo bone formation. Strategies using simple chemistry to control complex biological processes would be particularly powerful, as they make production of therapeutic materials simpler and more easily controlled.

show abstract

Regulation of bone matrix protein expression and induction of differentiation of human osteoblasts and human bone marrow stromal cells by bone morphogenetic protein-2

Cited by 246 publications

References 55 publications

Teriparatide (Human Parathyroid Hormone (1–34)) Inhibits Osteogenic Vascular Calcification in Diabetic Low Density Lipoprotein Receptor-deficient Mice

Teriparatide (Human Parathyroid Hormone (1–34)) Inhibits Osteogenic Vascular Calcification in Diabetic Low Density Lipoprotein Receptor-deficient Mice

The Mechanism of Phosphorus as a Cardiovascular Risk Factor in CKD

Active multilayered capsules for in vivo bone formation

Contact Info

Product

Resources

About