The role of alkaline phosphatase in cartilage mineralization

Golub, Ellis E.; Harrison, Greg J.; Taylor, Andrew G.; Camper, Sally A.; Shapiro, Irving M.

doi:10.1016/0169-6009(92)90750-8

Cited by 111 publications

(79 citation statements)

References 9 publications

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“…The results are expressed as percent control (mmole p-nitrophenol/min/mg protein). This method has been described in detail in an earlier publication (Golub et al, 1992).…”

Section: Alkaline Phosphatase Activitymentioning

confidence: 99%

Expression of HIF prolyl hydroxylase isozymes in growth plate chondrocytes: Relationship between maturation and apoptotic sensitivity

Terkhorn

Bohensky

Shapiro

et al. 2006

Journal Cellular Physiology

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The overall goal of the current study was to examine the functional activity of the prolyl hydroxylases (PHDs) in maturing chondrocytes. Herein, we show for the first time that the PHDs are expressed in the maturing zone of the growth plate, and by a chondrocytic cell line. We determined if this protein and its substrate, hypoxia inducible factor (HIF)-1a, modulated the induction of apoptosis. Using a chondrocyte cell line that matured in culture, we inhibited HIF-1a expression using siRNA technology and pharmacologically blocked PHD activity. We noted that PHD suppression sensitized the cells to an apoptotic challenge with H 2 O 2 . We next examined the interplay between the PHDs and HIF-1a by suppressing HIF-1a and blocking PHD activity. We noted reduced killing when the mature HIF-silenced cells were challenged with H 2 O 2 . In contrast, there was limited change in the viability of immature cells. Based on these differences in chondrocyte susceptibility, it is concluded that HIF-1a sensitizes maturing cells to H 2 O 2 -mediated killing. We next determined if this change in the viability of the PHD-inhibited cells was linked to changes in activation of caspase-3. It was noted that there was a minimal change in enzyme activity of the PHD-inhibited HIF-1a suppressed cells. Finally, we found that as the chondrocytes mature, the activities of catalase and SOD were significantly reduced and that there was a decrease in the levels of Bcl-2 and Bcl XL . This loss of protective activity together with the changes mediated by HIF would be expected to generate conditions that would favor the induction of chondrocyte apoptosis.

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“…The results are expressed as percent control (mmole p-nitrophenol/min/mg protein). This method has been described in detail in an earlier publication (Golub et al, 1992).…”

Section: Alkaline Phosphatase Activitymentioning

confidence: 99%

Expression of HIF prolyl hydroxylase isozymes in growth plate chondrocytes: Relationship between maturation and apoptotic sensitivity

Terkhorn

Bohensky

Shapiro

et al. 2006

Journal Cellular Physiology

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“…The enzyme alkaline phosphatase hydrolyses monophosphate esters in bone and cartilage tissue, releasing free phosphate, which, along with free calcium, is required for the formation of hydroxyl apatite (Robison 1923;Golub et al 1992). In thyroid cartilage alkaline phosphatase-positive chondrocytes occur for the first .…”

Section: Discussionmentioning

confidence: 99%

Androgen receptors and gender-specific distribution of alkaline phosphatase in human thyroid cartilage

Claassen

Mönig

Sel

et al. 2006

Histochem Cell Biol

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The degree of mineralization in human thyroid cartilage is gender specific. Until now, laryngeal tissue was tested for sexual hormone receptors by the use of radiolabelled hormones only without exact localization of the receptors. In this study immediately frozen cartilage specimens from seven male and one female patient who underwent laryngectomy were used for immunolocalization of sexual hormone receptors. Additionally, serum sexual hormone levels were measured by means of radioimmunoassay. Alkaline phosphatase was localized enzymohistochemically in another cohort of six male and four female cartilage specimens from laryngectomies and autopsies. Chondrocytes in thyroid cartilage from both sexes reacted with antibodies to the androgen receptor. The low serum testosterone levels, which varied between 1.5 and 3.9 ng/ml, did not correlate with insufficient mineralization of thyroid cartilage in men (r=0.363, P=0.432). Chondrocytes did not react with antibodies to the estrogen receptor alpha and the progesterone receptor in both sexes. Expression of alkaline phosphatase started about the middle of the second decade. Some chondrocytes near the mineralization front were positive for androgen receptor and alkaline phosphatase, other chondrocytes were negative for both. Our results suggest the involvement of androgen receptor positive chondrocytes in thyroid cartilage mineralization, probably by a testosterone-linked stimulation of alkaline phosphatase.

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“…ALPs are membrane-bound metalloenzymes suggested to play an active role in calcium deposition by decreasing levels of pyrophosphate, a calcification inhibitor 8 , and increasing levels of inorganic phosphate, which promotes mineralization [20]. ALP is highly expressed in human AVS through a complex cascade involving proinflammatory cytokines and factors [20][21][22] and is thought to play a prominent role in calcium deposition [21].…”

Section: Discussionmentioning

confidence: 99%

Assessing Calcification Onset in Aortic Valve Interstitial Cells

Khan¹,

B²,

Al‐Kindi³

et al. 2017

Cardiovasc Pharm Open Access

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IntroductionAortic valve stenosis (AVS) is a complex disease, characterized by the thickening of the aortic valve with significant fibrosis and/or calcification [1]. Short-term symptoms include shortness of breath and fainting, while more long-term symptoms include heart failure and inevitably, death [2]. Treatment for AVS remains non-existent, with surgical intervention being the only viable option for at-risk patients. Thus, there has been interest in finding innovative approaches to treating this perilous disease [3,4].The pathogenesis of AVS is an active process involving multiple cell types and complexed underlying mechanisms [5,6]. Upon differentiation of mesenchymal-like cells to chondrogenic cells, matrix vesicles are released, containing enzymes and other factors that lead to the onset of calcification [7]. One of these enzymes, alkaline phosphatase (ALP), is a metalloenzyme that has been shown to play a profound role in calcification onset by concentrating calcium [8], mineralizing hydroxyapatite crystals [8], and inactivating inhibitory polyphosphates [9]. In humans, there are four ALP isozymes: alkaline phosphatase, tissue-nonspecific isozyme (TNALP), intestinal-type alkaline phosphatase, placental-type alkaline phosphatase, and placental-like alkaline phosphatase [10]. Two isoforms of TNALP exist: bone-specific TNALP and liver-specific TNALP, both of which are abundantly found in the serum [10]. Within the context of vascular calcification, bone TNALP is highly expressed in calcifying vascular smooth muscle cells and is likely to be responsible for calcium deposition and AVS pathogenesis [10].A multitude of studies draw conclusions regarding the pathogenesis of AVS in humans by utilizing aortic valve interstitial cells from bovine [11][12][13]. The ultimate goal of these studies is to identify mechanisms that will help us better understand calcification onset in humans. However, there is a need to directly compare these animal models to humans and assess whether or not it is plausible to make such a AbstractAortic valve stenosis (AVS) is one of the most common heart valve diseases, and surgical intervention remains the only viable treatment option. Thus, there is a need for novel and innovative treatments. One approach is to study the biological pathogenesis of this disease in hopes of finding new targets for drug therapy. Although this may be a viable option, it faces some methodological concerns. Many studies attempted to address the underlying mechanisms of this disease using aortic valves from bovine models. Although these may be viable models in certain diseased conditions, this may not be the case when studying calcification in AVS. Thus, the aim of our study was to assess the significance of drawing conclusions from bovine models to humans in the context of AVS, and investigate the role of alkaline phosphatase (ALP), an enzyme that increases calcium mineralization and deposition in aortic valve calcification. We also wanted to identify any differences in calcification when using different os...

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The role of alkaline phosphatase in cartilage mineralization

Cited by 111 publications

References 9 publications

Expression of HIF prolyl hydroxylase isozymes in growth plate chondrocytes: Relationship between maturation and apoptotic sensitivity

Expression of HIF prolyl hydroxylase isozymes in growth plate chondrocytes: Relationship between maturation and apoptotic sensitivity

Androgen receptors and gender-specific distribution of alkaline phosphatase in human thyroid cartilage

Assessing Calcification Onset in Aortic Valve Interstitial Cells

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