Vitamin D-resistant rickets associated withepidermal nevus syndrome: Demonstration of a phosphaturic substance in the dermal lesions

Aschinberg, Lorenzo C.; Solomon, Lawrence M.; Zeis, Petros M.; Justice, Parvin; Rosenthal, Ira M.

doi:10.1016/s0022-3476(77)80444-7

Cited by 175 publications

(94 citation statements)

References 12 publications

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“…Several groups have attempted to characterize the putative phosphaturic factor by different approaches. For example, extracts from OOM tumors were shown to be phosphaturic when injected into dogs, rats or mice, and to inhibit the production of 1,25(OH) 2 D 3 in primary kidney cell cultures (Aschinberg et al 1977, Lau et al 1979, Popovtzer 1981, Miyauchi et al 1988. Others have shown that conditioned medium from primary cultures of tumor cells inhibits phosphate uptake by opossum kidney (OK) cells (Cai et al 1994, Wilkins et al 1995, Nelson et al 1996.…”

Section: Introductionmentioning

confidence: 99%

Extracts from tumors causing oncogenic osteomalacia inhibit phosphate uptake in opossum kidney cells

Jonsson

Mannstadt²,

Miyauchi³

et al. 2001

Journal of Endocrinology

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In oncogenic osteomalacia (OOM), a tumor produces an unknown substance that inhibits phosphate reabsorption in the proximal tubules. This causes urinary phosphate wasting and, as a consequence, hypophosphatemic osteomalacia. To characterize this poorly understood biological tumor activity we generated aqueous extracts from several OOM tumors. Extracts from three of four tumors inhibited, dose-and time-dependently, 32 Porthophosphate uptake by opossum kidney (OK) cells; maximum inhibition was about 45% of untreated control. Further characterization revealed that the factor is resistant to heat and several proteases, and that it has a low molecular weight. The tumor extracts also stimulated cAMP accumulation in OK cells, but not in osteoblastic ROS 17/2·8 and UMR106 cells, or in LLC-PK1 kidney cells expressing the parathyroid hormone (PTH)/PTHrelated peptide receptor or the PTH-2 receptor. HPLC separation of low molecular weight fractions of the tumor extracts revealed that the flow-through of all three positive tumor extracts inhibited 32 P uptake and stimulated cAMP accumulation in OK cells. Additionally, a second peak with inhibitory activity on phosphate transport, but without cAMP stimulatory activity, was identified in the most potent tumor extract. We have concluded that several low molecular weight molecules with the ability to inhibit phosphate transport in OK cells can be found in extracts from OOM tumors. It remains uncertain, however, whether these are related to the long-sought phosphaturic factor responsible for the phosphate wasting seen in OOM patients.

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Section: Introductionmentioning

confidence: 99%

Extracts from tumors causing oncogenic osteomalacia inhibit phosphate uptake in opossum kidney cells

Jonsson

Mannstadt²,

Miyauchi³

et al. 2001

Journal of Endocrinology

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“…42 The existence of a phosphatonin system in dogs comparable to that in humans was suggested by an early study in which a 6-week-old puppy developed phosphaturia after being injected with an extract from a tumor that caused TIO in a human patient. 8 This result suggests that a phosphatonin bone-renal axis probably occurs in the dog.…”

Section: Fibroblast Growth Factor 23 In Domestic Animals: What We Knomentioning

confidence: 84%

Fibroblast Growth Factor 23

Hardcastle¹,

Dittmer

2015

Vet Pathol

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Traditionally, control of phosphorus in the body has been considered secondary to the tighter control of calcium by parathyroid hormone and vitamin D. However, over the past decade, substantial advances have been made in understanding the control of phosphorus by the so-called phosphatonin system, the lynchpin of which is fibroblast growth factor 23 (FGF23). FGF23 binds to the klotho/FGFR1c receptor complex in renal tubular epithelial cells, leading to upregulation of Na/P i cotransporters and subsequent excretion of phosphorus from the body. In addition, FGF23 inhibits parathyroid hormone and the renal 1a-hydroxylase enzyme, while it stimulates 24-hydroxylase, leading to decreased 1,25-dihydroxyvitamin D 3 . FGF23 is intimately involved in the pathogenesis of a number of diseases, particularly the hereditary hypophosphatemic rickets group and chronic kidney disease, and is a target for the development of new treatments in human medicine. Little work has been done on FGF23 or the other phosphatonins in veterinary medicine, but increases in FGF23 are seen with chronic kidney disease in cats, and increased FGF23 expression has been found in soft tissue sarcomas in dogs.Keywords fibroblast growth factor 23, phosphatonin, phosphorus metabolism disorders, rickets, chronic renal failure, chronic kidney disease Fibroblast growth factor 23 (FGF23) is a recently recognized hormone that plays an intrinsic role in calcium and phosphorus metabolism, both in health and disease. Studies have shown that in humans, FGF23 is implicated in multiple inherited bone diseases, paraneoplastic bone disease (tumor-induced osteomalacia), and complications of chronic kidney disease and cardiovascular disease. In animals, a handful of studies have already recognized potential roles for FGF23 as a biomarker of disease and perhaps as a therapeutic agent. This review details the manner in which FGF23 joins established players in calciumphosphorus metabolism, current knowledge of its role in disease in humans and animals, and future avenues for research and use of this hormone.

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“…Abnormalities in the eyes, heart, or genitourinary system have also been reported (112). Hypophosphataemic rickets is rare (113)(114)(115) in ENS; the manifestation usually presents in the first years of life (114,116). It is generally accepted that it may represent a variant of tumor-induced rickets/osteomalacia (113)(114)(117)(118) characterized by renal phosphate wasting and inappropriately low serum levels of 1, 25(OH)2D.…”

Section: Linear Nevus Sebaceous Syndrome (Lnss)mentioning

confidence: 99%

FGF23 and Phosphate Wasting Disorders

2013

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A decade ago, only two hormones, parathyroid hormone and 1,25(OH)2D, were widely recognized to directly affect phosphate homeostasis. Since the discovery of fibroblast growth factor 23 (FGF23) in 2000 (1), our understanding of the mechanisms of phosphate homeostasis and of bone mineralization has grown exponentially. FGF23 is the link between intestine, bone, and kidney together in phosphate regulation. However, we still do not know the complex mechanism of phosphate homeostasis and bone mineralization. The physiological role of FGF23 is to regulate serum phosphate. Secreted mainly by osteocytes and osteoblasts in the skeleton (2-3), it modulates kidney handling of phosphate reabsorption and calcitriol production. Genetic and acquired abnormalities in FGF23 structure and metabolism cause conditions of either hyper-FGF23 or hypo-FGF23. Hyper-FGF23 is related to hypophosphatemia, while hypo-FGF23 is related to hyperphosphatemia. Both hyper-FGF23 and hypo-FGF23 are detrimentalto humans. In this review, we will discuss the pathophysiology of FGF23 and hyper-FGF23 related renal phosphate wasting disorders (4 IntroductionAccording to pathogenesis, ricketsis classified into calicopenic rickets, phosphopenicrickets, and a miscellaneous group associated with direct inhibitors of mineralization ( 5). In general, most instances of nutritional rickets are calicopenic, whereas heritable causes are usually phosphopenic. In this review we focus on hypophosphatemic rickets or osteomalacia. The causes of hypophosphatemia are various, of whichthe most prominent one is decreased reabsorption of phosphate in the proximal tubule.Although renal tubular disease can result in excessive renal phosphate wasting, in most hypophosphatemic disordersno abnormalities are found in the proximal tubule (6-7). It is speculated that an unknown factor is responsible for this phenomenon. The discovery of fibroblast growth factor 23 (FGF23), a member of the Phosphate homeostasisPhosphate comprises about 1% of total body weight. About 85% of total body phosphate resides in the bone, 14% in the cells, and only 1% in the serum and extracellular fluids. Maintenance of serum phosphate within its normal range allows for optimal mineralization of bone without deposition in vascular and other soft tissues. Serum phosphate concentration is determined Xianglan Huang et al. www.boneresearch.org | Bone Research 121by the balance among intestinal absorption of phosphate from the diet, its storage in bone, and its excretion in the urine. The proximal tubule is responsible for the reabsorption of phosphate filtered at the glomerulus and is the primary regulator of phosphate balance in the body. Transportation in the proximal tubule is driven primarily by sodium-potassium ATPase, which is located in the baso-lateral membrane of the cell (8-11). Under normal conditions, about 85% of the filtered phosphate is reabsorbed via the sodium-phosphate co-transporter (NaPi2a and NaPi2c) in the proximal tubule (9, 11). Parathyroid hormone (PTH) is one of the most potent horm...

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Vitamin D-resistant rickets associated withepidermal nevus syndrome: Demonstration of a phosphaturic substance in the dermal lesions

Cited by 175 publications

References 12 publications

Extracts from tumors causing oncogenic osteomalacia inhibit phosphate uptake in opossum kidney cells

Extracts from tumors causing oncogenic osteomalacia inhibit phosphate uptake in opossum kidney cells

Fibroblast Growth Factor 23

FGF23 and Phosphate Wasting Disorders

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