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Gene Review

ATRNL1  -  attractin-like 1

Homo sapiens

Synonyms: ALP, Attractin-like protein 1, FLJ45344, KIAA0534, bA338L11.1, ...
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Disease relevance of ATRNL1

  • METHODS: Patients with knee arthritis (not due to gout, osteoarthritis, or septic arthritis) were randomized over 3 treatment arms: ALC, ALP, and JAC [1].
  • Alendronate-treated women with at least a 30% reduction in bone ALP had a lower risk of non-spine (RH = 0.72; CI: 0.55, 0.92) and hip fractures (RH = 0.26; CI: 0.08, 0.83) relative to those with reductions <30% [2].
  • Osteocalcin (OC) in the serum and total alkaline phosphatase (total ALP) in the serum, cortical and trabecular bone samples as bone formation markers, and C-terminal cross-linking telopeptide of type I collagen (CTX) in the serum and urine as bone resorption markers were measured [3].
  • Hypophosphatasia is an inherited disorder characterised by defective bone mineralisation and deficiency of serum and tissue liver/bone/kidney alkaline phosphatase (L/B/K ALP) activity [4].
  • The 3-year OS post-ASCT was 56% with improved outcome predicted by a better performance status (P=0.08), normal ALP (P=0.08), nephrotic syndrome (P=0.01) and the absence of severe hypotension (P=0.01) [5].

High impact information on ATRNL1

  • Results: ZOL maintained the mean level of total ALP at the middle of the reference range, whereas those treated with risedronate showed a linear increase in total ALP from the 6-month post-treatment time-point [6].
  • Here, we used mutagenesis, kinetic analysis, and computer modeling to identify the residues important for the binding of known ALP inhibitors to the TNALP active site [7].
  • MATERIALS AND METHODS: We measured biochemical markers of bone turnover (bone-specific alkaline phosphatase [bone ALP], intact N-terminal propeptide of type I collagen, and C-terminal crosslinked telopeptide of type 1 collagen) and BMD of the spine and hip at baseline and after 1 year of alendronate or placebo [2].
  • A type I collagen synthesis inhibitor L-azetidine-2-carboxylic acid, as well as osteocalcin (OCN), significantly antagonized Smad3-stimulated ALP activity and mineralization of MC3T3-E1 cells [8].
  • ALP activity was synergistically increased by the treatment with a specific MEK-1 inhibitor PD98059 and rhBMP-2 in both cell lines [9].

Chemical compound and disease context of ATRNL1


Biological context of ATRNL1

  • Although this strong SMF exposure did not affect cell proliferation, it up-regulated cell differentiation and matrix synthesis as determined by ALP and alizarin red stainings, respectively [15].
  • We show that HS can increase the expression Runx2, ALP, and OPN in preosteoblast cells, suggesting the potential for exogenous HS to shift cells from proliferative to differentiative phenotypes [16].
  • Serum bone-specific alkaline phosphatase (S-bone ALP) and serum osteocalcin (S-OC) were assessed as markers of bone formation [17].
  • Scaffolds were then cultured to evaluate cell adhesion and ALP activity in vitro [18].
  • The DNA analysis revealed that the cells of the control group and the HOP-26 positive cells showed a 5 times higher cell growth compared to the STRO-1 and ALP positive cells [19].

Anatomical context of ATRNL1

  • When administered at intermediate stages of osteoblast differentiation (days 12, 15 and 18) BSP remained refractory to rhOP-1 whereas the ALP was increased almost 2-fold, independent of the constitutive levels of mRNA expression [20].
  • Changes were comparable but more pronounced in the tibia group, and marker concentrations remained increased at the end of study (bone ALP, 86 vs 74 U/L; OC, 14.9 vs 7.7 mug/L; ICTP: 5.6 vs 3.3 mug/L at day 84 after osteosynthesis, P <0.05 in tibia; 80 vs 70 U/L, 8 vs 5.2 mug/L, and 3.5 vs 3.2 mug/L, respectively, in the malleolar fracture group) [21].
  • RESULTS: In intact articular cartilage, ALP accumulated to a significantly higher degree than myoglobin [22].
  • The L/B/K ALP transcript, expressed in fetal rat small intestine, also contained the bone-type leader exon [23].
  • Calvaria treated with homogenates of normal dog salivary gland, kidney, bladder, and muscle did not increase ALP activity [24].

Associations of ATRNL1 with chemical compounds

  • The change in ALP and bilirubin observed from the precholangiographic value up to 2 and 12 months afterward was not significantly different in those with and without DS [25].
  • Vitamin A is a potent inducer for liver/bone/kidney alkaline phosphatase (L/B/K ALP) in a variety of tissues [23].
  • Overall, a significant treatment effect was observed for DPD (between-group difference 16.0%; 95%CI, 10.9 to 21.1), CTX (29.9%; 95%CI, 23.3 to 36.5), and bone ALP (13.2%; 95%CI, 6.6 to 19.7) after 24 weeks [26].
  • Testosterone had no effect on ALP activity nor calcium deposition in either sex [27].
  • Treatment of IEC-6 cells with all-trans retinoic acid (RA) increased the levels of activity, protein and mRNA of L/B/K ALP, whereas enterocyte-specific proteins, including intestinal ALP, sucrase-isomaltase and glucose transporter-2, were not induced [23].

Analytical, diagnostic and therapeutic context of ATRNL1

  • OBJECTIVE: To compare the efficacy of arthroscopic lavage plus administration of corticosteroids (ALC), arthroscopic lavage plus administration of placebo (ALP), and joint aspiration plus administration of corticosteroids (JAC) in knee arthritis, and to evaluate whether clinical or histologic characteristics determine outcome [1].
  • ALP scintigraphy may represent a functional assay for early, premorphological cartilage alterations in human arthritis as well [22].
  • In conclusion, these results suggest that BALP measurement with this immunoassay may be clinically useful, and more sensitive than total ALP, in the assessment of bone turnover during changes of the estrogen status as well as in monitoring the effects of treatments that modify the metabolic activity of the skeleton [28].
  • METHODS: ALP isoforms were separated using cellulose acetate electrophoresis and the activity was demonstrated using indolyl blue reagent [29].
  • High-performance liquid chromatography (HPLC) separates three human bone alkaline phosphatase (BALP) isoforms in serum; two major BALP isoforms, B1 and B2, and a minor fraction, B/I, which is composed on average of 70% bone and 30% intestinal ALP [30].


  1. Comparison of efficacy of arthroscopic lavage plus administration of corticosteroids, arthroscopic lavage plus administration of placebo, and joint aspiration plus administration of corticosteroids in arthritis of the knee: A randomized controlled trial. van Oosterhout, M., Sont, J.K., Bajema, I.M., Breedveld, F.C., van Laar, J.M. Arthritis Rheum. (2006) [Pubmed]
  2. Change in bone turnover and hip, non-spine, and vertebral fracture in alendronate-treated women: the fracture intervention trial. Bauer, D.C., Black, D.M., Garnero, P., Hochberg, M., Ott, S., Orloff, J., Thompson, D.E., Ewing, S.K., Delmas, P.D. J. Bone Miner. Res. (2004) [Pubmed]
  3. Low-level lifetime exposure to cadmium decreases skeletal mineralization and enhances bone loss in aged rats. Brzóska, M.M., Moniuszko-Jakoniuk, J. Bone (2004) [Pubmed]
  4. Identification of fifteen novel mutations in the tissue-nonspecific alkaline phosphatase (TNSALP) gene in European patients with severe hypophosphatasia. Mornet, E., Taillandier, A., Peyramaure, S., Kaper, F., Muller, F., Brenner, R., Bussière, P., Freisinger, P., Godard, J., Le Merrer, M., Oury, J.F., Plauchu, H., Puddu, R., Rival, J.M., Superti-Furga, A., Touraine, R.L., Serre, J.L., Simon-Bouy, B. Eur. J. Hum. Genet. (1998) [Pubmed]
  5. Autologous stem cell transplantation in primary systemic amyloidosis: the impact of selection criteria on outcome. Mollee, P.N., Wechalekar, A.D., Pereira, D.L., Franke, N., Reece, D., Chen, C., Stewart, A.K. Bone Marrow Transplant. (2004) [Pubmed]
  6. Long-Term Control of Bone Turnover in Paget's Disease With Zoledronic Acid and Risedronate. Hosking, D., Lyles, K., Brown, J.P., Fraser, W.D., Miller, P., Diaz Curiel, M., Devogelaer, J.P., Hooper, M., Su, G., Zelenakas, K., Pak, J., Fashola, T., Saidi, Y., Fink Eriksen, E., Reid, I.R. J. Bone Miner. Res. (2007) [Pubmed]
  7. Residues determining the binding specificity of uncompetitive inhibitors to tissue-nonspecific alkaline phosphatase. Kozlenkov, A., Le Du, M.H., Cuniasse, P., Ny, T., Hoylaerts, M.F., Millán, J.L. J. Bone Miner. Res. (2004) [Pubmed]
  8. Smad3 promotes alkaline phosphatase activity and mineralization of osteoblastic MC3T3-E1 cells. Sowa, H., Kaji, H., Yamaguchi, T., Sugimoto, T., Chihara, K. J. Bone Miner. Res. (2002) [Pubmed]
  9. Continuous inhibition of MAPK signaling promotes the early osteoblastic differentiation and mineralization of the extracellular matrix. Higuchi, C., Myoui, A., Hashimoto, N., Kuriyama, K., Yoshioka, K., Yoshikawa, H., Itoh, K. J. Bone Miner. Res. (2002) [Pubmed]
  10. Short-term effects of new synthetic conjugated estrogens on biochemical markers of bone turnover. Garnero, P., Stevens, R.E., Ayres, S.A., Phelps, K.V. Journal of clinical pharmacology. (2002) [Pubmed]
  11. How often are liver function tests normal in acute biliary pancreatitis? Dholakia, K., Pitchumoni, C.S., Agarwal, N. J. Clin. Gastroenterol. (2004) [Pubmed]
  12. A hepatoma-associated alkaline phosphatase, the Kasahara isozyme, compared with one of the isozymes of FL amnion cells. Higashino, K., Kudo, S., Otani, R., Yamamura, Y. Ann. N. Y. Acad. Sci. (1975) [Pubmed]
  13. Short-term treatment with troglitazone decreases bone turnover in patients with type 2 diabetes mellitus. Okazaki, R., Miura, M., Toriumi, M., Taguchi, M., Hirota, Y., Fukumoto, S., Fujita, T., Tanaka, K., Takeuchi, A. Endocr. J. (1999) [Pubmed]
  14. Resistance to alkyl-lysophospholipid-induced apoptosis due to downregulated sphingomyelin synthase 1 expression with consequent sphingomyelin- and cholesterol-deficiency in lipid rafts. Van der Luit, A.H., Budde, M., Zerp, S., Caan, W., Klarenbeek, J.B., Verheij, M., Van Blitterswijk, W.J. Biochem. J. (2007) [Pubmed]
  15. Strong static magnetic field stimulates bone formation to a definite orientation in vitro and in vivo. Kotani, H., Kawaguchi, H., Shimoaka, T., Iwasaka, M., Ueno, S., Ozawa, H., Nakamura, K., Hoshi, K. J. Bone Miner. Res. (2002) [Pubmed]
  16. Heparan sulfate regulates the anabolic activity of MC3T3-E1 preosteoblast cells by induction of Runx2. Jackson, R.A., Murali, S., van Wijnen, A.J., Stein, G.S., Nurcombe, V., Cool, S.M. J. Cell. Physiol. (2007) [Pubmed]
  17. Increased bone density and decreased bone turnover, but no evident alteration of fracture susceptibility in elderly women with diabetes mellitus. Gerdhem, P., Isaksson, A., Akesson, K., Obrant, K.J. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. (2005) [Pubmed]
  18. Performance of collagen sponge as a 3-D scaffold for tooth-tissue engineering. Sumita, Y., Honda, M.J., Ohara, T., Tsuchiya, S., Sagara, H., Kagami, H., Ueda, M. Biomaterials (2006) [Pubmed]
  19. Enrichment of osteogenic cell populations from rat bone marrow stroma. van den Dolder, J., Jansen, J.A. Biomaterials (2007) [Pubmed]
  20. Effects of osteogenic protein-1 (OP-1, BMP-7) on bone matrix protein expression by fetal rat calvarial cells are differentiation stage specific. Li, I.W., Cheifetz, S., McCulloch, C.A., Sampath, K.T., Sodek, J. J. Cell. Physiol. (1996) [Pubmed]
  21. Changes in biochemical markers after lower limb fractures. Stoffel, K., Engler, H., Kuster, M., Riesen, W. Clin. Chem. (2007) [Pubmed]
  22. Rat antigen-induced arthritis: cartilage alterations assessed with iodine-123-antileukoproteinase. Kinne, R.W., Meyer, P., Gründer, W., Buchner, E., Palombo-Kinne, E., Heinzel-Wieland, R., Becker, W., Wolf, F., Kalden, J.R., Burkhardt, H. J. Nucl. Med. (1998) [Pubmed]
  23. Vitamin A up-regulates expression of bone-type alkaline phosphatase in rat small intestinal crypt cell line and fetal rat small intestine. Nikawa, T., Rokutan, K., Nanba, K., Tokuoka, K., Teshima, S., Engle, M.J., Alpers, D.H., Kishi, K. J. Nutr. (1998) [Pubmed]
  24. Canine prostate stimulates osteoblast function using the endothelin receptors. LeRoy, B.E., Sellers, R.S., Rosol, T.J. Prostate (2004) [Pubmed]
  25. Dominant strictures in patients with primary sclerosing cholangitis. Björnsson, E., Lindqvist-Ottosson, J., Asztely, M., Olsson, R. Am. J. Gastroenterol. (2004) [Pubmed]
  26. Restoration of euthyroidism accelerates bone turnover in patients with subclinical hypothyroidism: a randomized controlled trial. Meier, C., Beat, M., Guglielmetti, M., Christ-Crain, M., Staub, J.J., Kraenzlin, M. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. (2004) [Pubmed]
  27. Estrogen receptor alpha genotype confers interindividual variability of response to estrogen and testosterone in mesenchymal-stem-cell-derived osteoblasts. Leskel??, H.V., Olkku, A., Lehtonen, S., Mahonen, A., Koivunen, J., Turpeinen, M., Uusitalo, J., Pelkonen, O., Kangas, L., Selander, K., Lehenkari, P. Bone (2006) [Pubmed]
  28. Clinical observations with a new specific assay for bone alkaline phosphatase: a cross-sectional study in osteoporotic and pagetic subjects and a longitudinal evaluation of the response to ovariectomy, estrogens, and bisphosphonates. Pedrazzoni, M., Alfano, F.S., Girasole, G., Giuliani, N., Fantuzzi, M., Gatti, C., Campanini, C., Passeri, M. Calcif. Tissue Int. (1996) [Pubmed]
  29. Clinical value of biliary alkaline phosphatase in non-jaundiced cholangiocarcinoma. Bhudhisawasdi, V., Muisuk, K., Areejitranusorn, P., Kularbkaew, C., Khampitak, T., Saeseow, O.T., Wongkham, S. J. Cancer Res. Clin. Oncol. (2004) [Pubmed]
  30. Differences in sialic acid residues among bone alkaline phosphatase isoforms: a physical, biochemical, and immunological characterization. Magnusson, P., Farley, J.R. Calcif. Tissue Int. (2002) [Pubmed]
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