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Gene Review

Pthlh  -  parathyroid hormone-like peptide

Mus musculus

Synonyms: PLP, PTH-like, PTH-rP, PTH-related peptide, PTHrP, ...
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Disease relevance of Pthlh


High impact information on Pthlh


Chemical compound and disease context of Pthlh


Biological context of Pthlh

  • In all 114 meiotic events examined, the Pthlh locus cosegregated with the locus for the Kirsten ras-2 gene (Kras-2) which was previously localized to distal mouse chromosome 6 [14].
  • These studies confirm the previous localization of Pthlh to mouse chromosome 6 using somatic cell hybrids and show that the Pthlh/PTHLH locus is a part of a conserved linkage group between distal mouse chromosome 6 and the proximal segment of the short arm of human chromosome 12 [14].
  • Together, the results suggest a model in which Ihh coordinates diverse aspects of skeletal morphogenesis through PTHrP-dependent and independent processes [15].
  • These findings establish a pivotal role for osteoblast-derived PTH-related protein (PTHrP) as a potent endogenous bone anabolic factor that potentiates bone formation by altering osteoblast recruitment and survival and whose level of expression in the bone microenvironment influences the therapeutic efficacy of exogenous PTH 1-34 [16].
  • The osteoporotic phenotype was recapitulated in mice with osteoblast-specific targeted disruption of Pthrp, generated using Cre-LoxP technology, and defective bone formation was reaffirmed as the underlying etiology [16].

Anatomical context of Pthlh


Associations of Pthlh with chemical compounds


Physical interactions of Pthlh


Regulatory relationships of Pthlh


Other interactions of Pthlh

  • Previously, we have shown that PTHrP also acts downstream of transforming growth factor beta (TGFbeta) in a common signaling cascade to regulate hypertrophic differentiation in embryonic mouse metatarsal organ cultures [27].
  • Furthermore, by regulating distal chondrocyte differentiation, Gli3 seems to position the domain of PTHrP expression [28].
  • In addition, the expression of tenascin C, another marker of the mammary mesenchyme, is also dependent on PTHrP [22].
  • Furthermore the expression of the Ihh target genes patched (Ptch) and PTHrP is reactivated in Ihh-/-;Gli3-/- mutants [28].
  • Multipotential mesenchymal cells (C3H10T1/2) transfected with normal or mutant PTH-1Rs and MC3T3-E1 osteoblastic cells were used to explore the roles of PTH, PTHrP, and the PTH-1R in cell viability relative to osteoblastic differentiation [29].

Analytical, diagnostic and therapeutic context of Pthlh


  1. Parathyroid hormone is essential for normal fetal bone formation. Miao, D., He, B., Karaplis, A.C., Goltzman, D. J. Clin. Invest. (2002) [Pubmed]
  2. Targeted overexpression of parathyroid hormone-related peptide in chondrocytes causes chondrodysplasia and delayed endochondral bone formation. Weir, E.C., Philbrick, W.M., Amling, M., Neff, L.A., Baron, R., Broadus, A.E. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  3. Parathyroid hormone-related protein is required for tooth eruption. Philbrick, W.M., Dreyer, B.E., Nakchbandi, I.A., Karaplis, A.C. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  4. Indian hedgehog coordinates endochondral bone growth and morphogenesis via parathyroid hormone related-protein-dependent and -independent pathways. Karp, S.J., Schipani, E., St-Jacques, B., Hunzelman, J., Kronenberg, H., McMahon, A.P. Development (2000) [Pubmed]
  5. Defining the roles of parathyroid hormone-related protein in normal physiology. Philbrick, W.M., Wysolmerski, J.J., Galbraith, S., Holt, E., Orloff, J.J., Yang, K.H., Vasavada, R.C., Weir, E.C., Broadus, A.E., Stewart, A.F. Physiol. Rev. (1996) [Pubmed]
  6. A mutant PTH/PTHrP type I receptor in enchondromatosis. Hopyan, S., Gokgoz, N., Poon, R., Gensure, R.C., Yu, C., Cole, W.G., Bell, R.S., Jüppner, H., Andrulis, I.L., Wunder, J.S., Alman, B.A. Nat. Genet. (2002) [Pubmed]
  7. Parathyroid hormone-related peptide is a naturally occurring, protein kinase A-dependent angiogenesis inhibitor. Bakre, M.M., Zhu, Y., Yin, H., Burton, D.W., Terkeltaub, R., Deftos, L.J., Varner, J.A. Nat. Med. (2002) [Pubmed]
  8. PTH/PTHrP receptor in early development and Indian hedgehog-regulated bone growth. Lanske, B., Karaplis, A.C., Lee, K., Luz, A., Vortkamp, A., Pirro, A., Karperien, M., Defize, L.H., Ho, C., Mulligan, R.C., Abou-Samra, A.B., Jüppner, H., Segre, G.V., Kronenberg, H.M. Science (1996) [Pubmed]
  9. The parathyroid hormone-related protein system and diabetic nephropathy outcome in streptozotocin-induced diabetes. Izquierdo, A., López-Luna, P., Ortega, A., Romero, M., Guitiérrez-Tarrés, M.A., Arribas, I., Alvarez, M.J., Esbrit, P., Bosch, R.J. Kidney Int. (2006) [Pubmed]
  10. Capecitabine improves cancer cachexia and normalizes IL-6 and PTHrP levels in mouse cancer cachexia models. Fujimoto-Ouchi, K., Onuma, E., Shirane, M., Mori, K., Tanaka, Y. Cancer Chemother. Pharmacol. (2007) [Pubmed]
  11. The calcium-sensing receptor regulates mammary gland parathyroid hormone-related protein production and calcium transport. VanHouten, J., Dann, P., McGeoch, G., Brown, E.M., Krapcho, K., Neville, M., Wysolmerski, J.J. J. Clin. Invest. (2004) [Pubmed]
  12. Role of parathyroid hormone-related protein in tubulointerstitial apoptosis and fibrosis after folic acid-induced nephrotoxicity. Ortega, A., Rámila, D., Ardura, J.A., Esteban, V., Ruiz-Ortega, M., Barat, A., Gazapo, R., Bosch, R.J., Esbrit, P. J. Am. Soc. Nephrol. (2006) [Pubmed]
  13. Parathyroid hormone-related protein induces spontaneous osteoclast formation via a paracrine cascade. Nakchbandi, I.A., Weir, E.E., Insogna, K.L., Philbrick, W.M., Broadus, A.E. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  14. Localization of mouse parathyroid hormone-like peptide gene (Pthlh) to distal chromosome 6 using interspecific backcross mice and in situ hybridization. Seldin, M.F., Mattei, M.G., Hendy, G.N. Cytogenet. Cell Genet. (1992) [Pubmed]
  15. Indian hedgehog signaling regulates proliferation and differentiation of chondrocytes and is essential for bone formation. St-Jacques, B., Hammerschmidt, M., McMahon, A.P. Genes Dev. (1999) [Pubmed]
  16. Osteoblast-derived PTHrP is a potent endogenous bone anabolic agent that modifies the therapeutic efficacy of administered PTH 1-34. Miao, D., He, B., Jiang, Y., Kobayashi, T., Sorocéanu, M.A., Zhao, J., Su, H., Tong, X., Amizuka, N., Gupta, A., Genant, H.K., Kronenberg, H.M., Goltzman, D., Karaplis, A.C. J. Clin. Invest. (2005) [Pubmed]
  17. Interaction of FGF, Ihh/Pthlh, and BMP signaling integrates chondrocyte proliferation and hypertrophic differentiation. Minina, E., Kreschel, C., Naski, M.C., Ornitz, D.M., Vortkamp, A. Dev. Cell (2002) [Pubmed]
  18. Indian hedgehog stimulates periarticular chondrocyte differentiation to regulate growth plate length independently of PTHrP. Kobayashi, T., Soegiarto, D.W., Yang, Y., Lanske, B., Schipani, E., McMahon, A.P., Kronenberg, H.M. J. Clin. Invest. (2005) [Pubmed]
  19. Transforming growth factor-beta stimulates mouse blastocyst outgrowth through a mechanism involving parathyroid hormone-related protein. Nowak, R.A., Haimovici, F., Biggers, J.D., Erbach, G.T. Biol. Reprod. (1999) [Pubmed]
  20. Parathyroid hormone-related peptide interacts with bone morphogenetic protein 2 to increase osteoblastogenesis and decrease adipogenesis in pluripotent C3H10T 1/2 mesenchymal cells. Chan, G.K., Miao, D., Deckelbaum, R., Bolivar, I., Karaplis, A., Goltzman, D. Endocrinology (2003) [Pubmed]
  21. Expression of a parathyroid hormone-like protein and its receptor during differentiation of embryonal carcinoma cells. Chan, S.D., Strewler, G.J., King, K.L., Nissenson, R.A. Mol. Endocrinol. (1990) [Pubmed]
  22. Parathyroid hormone-related protein signaling is necessary for sexual dimorphism during embryonic mammary development. Dunbar, M.E., Dann, P.R., Robinson, G.W., Hennighausen, L., Zhang, J.P., Wysolmerski, J.J. Development (1999) [Pubmed]
  23. Inhibition of terminal chondrocyte differentiation by bone morphogenetic protein 7 (OP-1) in vitro depends on the periarticular region but is independent of parathyroid hormone-related peptide. Haaijman, A., Karperien, M., Lanske, B., Hendriks, J., Löwik, C.W., Bronckers, A.L., Burger, E.H. Bone (1999) [Pubmed]
  24. PTHrP signaling targets cyclin D1 and induces osteoblastic cell growth arrest. Datta, N.S., Chen, C., Berry, J.E., McCauley, L.K. J. Bone Miner. Res. (2005) [Pubmed]
  25. Parathyroid hormone-related protein regulates extracellular matrix gene expression in cementoblasts and inhibits cementoblast-mediated mineralization in vitro. Ouyang, H., McCauley, L.K., Berry, J.E., Saygin, N.E., Tokiyasu, Y., Somerman, M.J. J. Bone Miner. Res. (2000) [Pubmed]
  26. BMP4 and PTHrP interact to stimulate ductal outgrowth during embryonic mammary development and to inhibit hair follicle induction. Hens, J.R., Dann, P., Zhang, J.P., Harris, S., Robinson, G.W., Wysolmerski, J. Development (2007) [Pubmed]
  27. TGFbeta2 mediates the effects of hedgehog on hypertrophic differentiation and PTHrP expression. Alvarez, J., Sohn, P., Zeng, X., Doetschman, T., Robbins, D.J., Serra, R. Development (2002) [Pubmed]
  28. Gli3 acts as a repressor downstream of Ihh in regulating two distinct steps of chondrocyte differentiation. Koziel, L., Wuelling, M., Schneider, S., Vortkamp, A. Development (2005) [Pubmed]
  29. Parathyroid hormone and parathyroid hormone-related protein exert both pro- and anti-apoptotic effects in mesenchymal cells. Chen, H.L., Demiralp, B., Schneider, A., Koh, A.J., Silve, C., Wang, C.Y., McCauley, L.K. J. Biol. Chem. (2002) [Pubmed]
  30. Response of immortalized murine cementoblasts/periodontal ligament cells to parathyroid hormone and parathyroid hormone-related protein in vitro. Ouyang, H., McCauley, L.K., Berry, J.E., D'Errico, J.A., Strayhorn, C.L., Somerman, M.J. Arch. Oral Biol. (2000) [Pubmed]
  31. Parathyroid hormone-related peptide as an endogenous inducer of parietal endoderm differentiation. van de Stolpe, A., Karperien, M., Löwik, C.W., Jüppner, H., Segre, G.V., Abou-Samra, A.B., de Laat, S.W., Defize, L.H. J. Cell Biol. (1993) [Pubmed]
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