insulin like growth factor binding protein 5


Summary: One of the six homologous soluble proteins that bind insulin-like growth factors (SOMATOMEDINS) and modulate their mitogenic and metabolic actions at the cellular level.

Top Publications

  1. Stolf B, Carvalho A, Martins W, Runza F, Brun M, Hirata R, et al. Differential expression of IGFBP-5 and two human ESTs in thyroid glands with goiter, adenoma and papillary or follicular carcinomas. Cancer Lett. 2003;191:193-202 pubmed
    ..IGFBP-5 and gene 44 were significantly overexpressed in papillary carcinoma when compared to normal and goiter. Genes 44 and 199 were differentially expressed in follicular carcinoma and adenoma when compared to normal thyroid tissue...
  2. Xu Q, Li S, Zhao Y, Maures T, Yin P, Duan C. Evidence that IGF binding protein-5 functions as a ligand-independent transcriptional regulator in vascular smooth muscle cells. Circ Res. 2004;94:E46-54 pubmed
    ..These results suggest that IGFBP-5 is localized in VSMC nucleus and possesses transcription-regulatory activity that is IGF independent. ..
  3. Mita K, Zhang Z, Ando Y, Toyama T, Hamaguchi M, Kobayashi S, et al. Prognostic significance of insulin-like growth factor binding protein (IGFBP)-4 and IGFBP-5 expression in breast cancer. Jpn J Clin Oncol. 2007;37:575-82 pubmed
  4. Cesi V, Vitali R, Tanno B, Giuffrida M, Sesti F, Mancini C, et al. Insulin-like growth factor binding protein 5: contribution to growth and differentiation of neuroblastoma cells. Ann N Y Acad Sci. 2004;1028:59-68 pubmed
    ..Given the relevance of IGF-2 in determining the proliferative and metastatic behavior of NB, the role of IGFBP-5 as a modulator of the IGF signal transduction pathway should be studied further for potential therapeutic applications. ..
  5. Amaar Y, Thompson G, Linkhart T, Chen S, Baylink D, Mohan S. Insulin-like growth factor-binding protein 5 (IGFBP-5) interacts with a four and a half LIM protein 2 (FHL2). J Biol Chem. 2002;277:12053-60 pubmed
    ..The role of FHL2 as an intracellular mediator of the effects of IGFBP-5 and other osteoregulatory agents in osteoblasts will need to be verified in future studies. ..
  6. Butt A, Dickson K, Jambazov S, Baxter R. Enhancement of tumor necrosis factor-alpha-induced growth inhibition by insulin-like growth factor-binding protein-5 (IGFBP-5), but not IGFBP-3 in human breast cancer cells. Endocrinology. 2005;146:3113-22 pubmed
    ..Furthermore, although IGFBP-3 and IGFBP-5 share much structural and functional homology, they can modulate distinct apoptotic pathways in human breast cancer cells. ..
  7. Marshman E, Green K, Flint D, White A, Streuli C, Westwood M. Insulin-like growth factor binding protein 5 and apoptosis in mammary epithelial cells. J Cell Sci. 2003;116:675-82 pubmed
    ..This study provides evidence that IGFBP-5 plays an important role in the regulation of apoptosis in the mammary gland. ..
  8. Hao X, Sun B, Hu L, Lähdesmäki H, Dunmire V, Feng Y, et al. Differential gene and protein expression in primary breast malignancies and their lymph node metastases as revealed by combined cDNA microarray and tissue microarray analysis. Cancer. 2004;100:1110-22 pubmed
    ..Therefore, gene expression profiling and tissue array validation should be combined to elucidate molecular events associated with the metastatic process. ..
  9. Tanno B, Negroni A, Vitali R, Pirozzoli M, Cesi V, Mancini C, et al. Expression of insulin-like growth factor-binding protein 5 in neuroblastoma cells is regulated at the transcriptional level by c-Myb and B-Myb via direct and indirect mechanisms. J Biol Chem. 2002;277:23172-80 pubmed
    ..Finally, IGFBP-5 was able to modulate proliferation of NB cells in a manner dependent on its concentration and on the presence of IGFs. ..

More Information


  1. Hyde C, Hollier B, Anderson A, Harkin D, Upton Z. Insulin-like growth factors (IGF) and IGF-binding proteins bound to vitronectin enhance keratinocyte protein synthesis and migration. J Invest Dermatol. 2004;122:1198-206 pubmed
    ..Moreover, these results suggest that IGF-II:VN and IGF-I:IGFBP-5:VN complexes may be useful in situations where enhanced keratinocyte cell migration and proliferation is required, such as in wound healing and skin regeneration. ..
  2. Cesi V, Giuffrida M, Vitali R, Tanno B, Mancini C, Calabretta B, et al. C/EBP alpha and beta mimic retinoic acid activation of IGFBP-5 in neuroblastoma cells by a mechanism independent from binding to their site. Exp Cell Res. 2005;305:179-89 pubmed
    ..Of interest, we found that both transcription factors were able to interact with the TATA box, but only C/EBPalpha interaction increased during RA-induced differentiation. ..
  3. Yeh L, Lee J. Identification of an osteogenic protein-1 (bone morphogenetic protein-7)-responsive element in the promoter of the rat insulin-like growth factor-binding protein-5 gene. Endocrinology. 2000;141:3278-86 pubmed
    ..In conclusion, we identified an OP-1 response region in the rat IGFBP-5 promoter and further showed that OP-1 down-regulates the nuclear protein interaction with the response element(s). ..
  4. Ständker L, Wobst P, Mark S, Forssmann W. Isolation and characterization of circulating 13-kDa C-terminal fragments of human insulin-like growth factor binding protein-5. FEBS Lett. 1998;441:281-6 pubmed
  5. Twigg S, Baxter R. Insulin-like growth factor (IGF)-binding protein 5 forms an alternative ternary complex with IGFs and the acid-labile subunit. J Biol Chem. 1998;273:6074-9 pubmed
    ..The demonstration of IGFBP-5-containing ternary complexes indicates an unrecognized form of IGF transport in the circulation and an additional mechanism for regulating IGF bioavailability. ..
  6. Wang H, Rosen D, Wang H, Fuller G, Zhang W, Liu J. Insulin-like growth factor-binding protein 2 and 5 are differentially regulated in ovarian cancer of different histologic types. Mod Pathol. 2006;19:1149-56 pubmed
    ..We concluded that IGFBP2 and IGFBP5 might play a role in the development of high-grade ovarian serous carcinoma, but not in mucinous or clear cell ovarian carcinomas. ..
  7. Tanno B, Vitali R, De Arcangelis D, Mancini C, Eleuteri P, Dominici C, et al. Bim-dependent apoptosis follows IGFBP-5 down-regulation in neuroblastoma cells. Biochem Biophys Res Commun. 2006;351:547-52 pubmed
    ..Of interest, Bim knock-down by siRNA decreases apoptosis in IGFBP-5-interfered cells. Thus, inhibition of endogenously produced IGFBP-5 is associated with Bim-dependent apoptosis in NB cells. ..
  8. Mukherjee A, Wilson E, Rotwein P. Insulin-like growth factor (IGF) binding protein-5 blocks skeletal muscle differentiation by inhibiting IGF actions. Mol Endocrinol. 2008;22:206-15 pubmed
  9. Allander S, Larsson C, Ehrenborg E, Suwanichkul A, Weber G, Morris S, et al. Characterization of the chromosomal gene and promoter for human insulin-like growth factor binding protein-5. J Biol Chem. 1994;269:10891-8 pubmed
  10. Amaar Y, Baylink D, Mohan S. Ras-association domain family 1 protein, RASSF1C, is an IGFBP-5 binding partner and a potential regulator of osteoblast cell proliferation. J Bone Miner Res. 2005;20:1430-9 pubmed
  11. Kiepe D, Ciarmatori S, Haarmann A, Tönshoff B. Differential expression of IGF system components in proliferating vs. differentiating growth plate chondrocytes: the functional role of IGFBP-5. Am J Physiol Endocrinol Metab. 2006;290:E363-71 pubmed
    ..These data suggest that the developmental stage of the chondrocyte is an important determinant of IGF and IGFBP expression and imply a functional role for IGFBP-5 for upregulating IGF action during chondrocyte differentiation in vivo. ..
  12. Massicotte F, Fernandes J, Martel Pelletier J, Pelletier J, Lajeunesse D. Modulation of insulin-like growth factor 1 levels in human osteoarthritic subchondral bone osteoblasts. Bone. 2006;38:333-41 pubmed
    ..These data suggest that increased IGF-1 levels correlate with elevated endogenous PGE2 levels in OA Ob and that higher IGF-1 levels in OA Ob could be important for bone sclerosis in OA. ..
  13. Takahashi M, Papavero V, Yuhas J, Kort E, Kanayama H, Kagawa S, et al. Altered expression of members of the IGF-axis in clear cell renal cell carcinoma. Int J Oncol. 2005;26:923-31 pubmed
    ..In addition, we demonstrate that the expression of the A isoform of the insulin receptor is significantly upregulated, while that of IGFBP-5 are significantly downregulated in this tumour subtype. ..
  14. Beattie J, Allan G, Lochrie J, Flint D. Insulin-like growth factor-binding protein-5 (IGFBP-5): a critical member of the IGF axis. Biochem J. 2006;395:1-19 pubmed
    ..We also examine the regulation of IGFBP-5 expression and comment on its potential role in tumour biology, with special reference to work with breast cancer cells. ..
  15. Busby W, Yocum S, Rowland M, Kellner D, Lazerwith S, Sverdrup F, et al. Complement 1s is the serine protease that cleaves IGFBP-5 in human osteoarthritic joint fluid. Osteoarthritis Cartilage. 2009;17:547-55 pubmed publisher
    ..Human OA fluid contains a serine protease that cleaves IGFBP-5. Zymography, immunoblotting and LC-MS/MS analysis indicate that C1s is the protease that accounts for this activity. ..
  16. McCaig C, Perks C, Holly J. Intrinsic actions of IGFBP-3 and IGFBP-5 on Hs578T breast cancer epithelial cells: inhibition or accentuation of attachment and survival is dependent upon the presence of fibronectin. J Cell Sci. 2002;115:4293-303 pubmed
    ..Our findings indicate that, in addition to being crucial modulators of IGF actions, the IGFBPs have direct actions on cell attachment and survival that are specific and dependent upon the matrix components present. ..
  17. Zhu X, Ling N, Shimasaki S. Cloning of the rat insulin- like growth factor binding protein-5 gene and DNA sequence analysis of its promoter region. Biochem Biophys Res Commun. 1993;190:1045-52 pubmed
    ..This finding suggests that the IGFBP-5 gene is one of those that are expressed in a tissue-specific manner. ..
  18. Butt A, Dickson K, McDougall F, Baxter R. Insulin-like growth factor-binding protein-5 inhibits the growth of human breast cancer cells in vitro and in vivo. J Biol Chem. 2003;278:29676-85 pubmed
    ..These data suggest that IGFBP-5 is a potent growth inhibitor and proapoptotic agent in human breast cancer cells via modulation of cell cycle regulation and apoptotic mediators. ..
  19. Kou K, Jenkins N, Gilbert D, Copeland N, Rotwein P. Organization, expression, and chromosomal location of the mouse insulin-like growth factor binding protein 5 gene. Genomics. 1994;20:412-8 pubmed
    ..Characterization of the mouse IGFBP-5 gene now provides a starting point for studying the roles and regulation of this protein in development. ..
  20. Ning Y, Hoang B, Schuller A, Cominski T, Hsu M, Wood T, et al. Delayed mammary gland involution in mice with mutation of the insulin-like growth factor binding protein 5 gene. Endocrinology. 2007;148:2138-47 pubmed
    ..These results demonstrate that IGFBP-5, although not essential for normal growth, is required for normal mammary gland involution and can regulate mammary gland morphogenesis in response to hormone stimulation. ..
  21. James P, Jones S, Busby W, Clemmons D, Rotwein P. A highly conserved insulin-like growth factor-binding protein (IGFBP-5) is expressed during myoblast differentiation. J Biol Chem. 1993;268:22305-12 pubmed
    ..Identification of an IGF-binding protein that is produced during myoblast differentiation provides a model system in which to study the potential modulatory role of IGFBPs in development. ..
  22. Ning Y, Schuller A, Bradshaw S, Rotwein P, Ludwig T, Frystyk J, et al. Diminished growth and enhanced glucose metabolism in triple knockout mice containing mutations of insulin-like growth factor binding protein-3, -4, and -5. Mol Endocrinol. 2006;20:2173-86 pubmed
  23. Salih D, Tripathi G, Holding C, Szestak T, Gonzalez M, Carter E, et al. Insulin-like growth factor-binding protein 5 (Igfbp5) compromises survival, growth, muscle development, and fertility in mice. Proc Natl Acad Sci U S A. 2004;101:4314-9 pubmed
  24. Matilainen M, Malinen M, Saavalainen K, Carlberg C. Regulation of multiple insulin-like growth factor binding protein genes by 1alpha,25-dihydroxyvitamin D3. Nucleic Acids Res. 2005;33:5521-32 pubmed
    ..In conclusion, IGFBP1, 3 and 5 are primary 1alpha,25(OH)2D3 target genes that in intact cells are each under the control of multiple VDREs. ..
  25. Liu Y, Sun W, Zhang K, Zheng H, Ma Y, Lin D, et al. Identification of genes differentially expressed in human primary lung squamous cell carcinoma. Lung Cancer. 2007;56:307-17 pubmed
    ..The differentially expressed genes reported in this study will provide a valuable resource for understanding the pathogenesis of lung SCCs and for discovery of novel diagnostic or therapeutic targets. ..
  26. Tonner E, Barber M, Allan G, Beattie J, Webster J, Whitelaw C, et al. Insulin-like growth factor binding protein-5 (IGFBP-5) induces premature cell death in the mammary glands of transgenic mice. Development. 2002;129:4547-57 pubmed
    ..It clearly demonstrates that IGF-I is an important developmental/survival factor for the mammary gland and, furthermore, this cell death programme may be utilised in a wide variety of tissues. ..
  27. Schedlich L, Le Page S, Firth S, Briggs L, Jans D, Baxter R. Nuclear import of insulin-like growth factor-binding protein-3 and -5 is mediated by the importin beta subunit. J Biol Chem. 2000;275:23462-70 pubmed
    ..Together these results suggest that the NLSs within the C-terminal domain of IGFBP-3 and IGFBP-5 are required for importin-beta-dependent nuclear uptake and probably also accumulation through mediating binding to nuclear components. ..
  28. Beattie J, Phillips K, Shand J, Szymanowska M, Flint D, Allan G. Molecular recognition characteristics in the insulin-like growth factor (IGF)-insulin-like growth factor binding protein -3/5 (IGFBP-3/5) heparin axis. J Mol Endocrinol. 2005;34:163-75 pubmed
    ..The potential biological significance of our data is highlighted by the demonstration that IGF-I and IGF-II can displace endogenous IGFBP-5 from monolayer cultures of the mouse mammary epithelial cell line HC11. ..
  29. Wang H, Arun B, Wang H, Fuller G, Zhang W, Middleton L, et al. IGFBP2 and IGFBP5 overexpression correlates with the lymph node metastasis in T1 breast carcinomas. Breast J. 2008;14:261-7 pubmed publisher
    ..Our data suggest that IGFBP2 and IGFBP5 play a role in the development of metastasis and may serve as useful markers to predict lymph node metastasis in patients with small (T1) invasive breast carcinomas. ..
  30. Jurgeit A, Berlato C, Obrist P, Ploner C, Massoner P, Schmölzer J, et al. Insulin-like growth factor-binding protein-5 enters vesicular structures but not the nucleus. Traffic. 2007;8:1815-28 pubmed
    ..The observation of nuclear uptake of IGFBP-5 was restricted to artificial conditions such as expression of non-secreted forms of IGFBP-5 or selective permeabilization of the plasma membrane by digitonin. ..
  31. Schneider M, Zhou R, Hoeflich A, Krebs O, Schmidt J, Mohan S, et al. Insulin-like growth factor-binding protein-5 inhibits growth and induces differentiation of mouse osteosarcoma cells. Biochem Biophys Res Commun. 2001;288:435-42 pubmed
    ..05) and secreted more osteocalcin protein than a mock clone or parental OS-50/K8 cells. Thus, part of the growth-inhibiting effect of IGFBP-5 may be due to an induction of differentiation in these cells. ..
  32. Iwanaga H, Matsumoto T, Enomoto H, Okano K, Hishikawa Y, Shindo H, et al. Enhanced expression of insulin-like growth factor-binding proteins in human osteoarthritic cartilage detected by immunohistochemistry and in situ hybridization. Osteoarthritis Cartilage. 2005;13:439-48 pubmed
    ..Up-regulation of IGFBPs as well as IGF-I and its receptor was observed for OA cartilage tissue, suggesting the involvement of IGFBPs in the pathogenesis of OA. ..
  33. Imai Y, Moralez A, Andag U, Clarke J, Busby W, Clemmons D. Substitutions for hydrophobic amino acids in the N-terminal domains of IGFBP-3 and -5 markedly reduce IGF-I binding and alter their biologic actions. J Biol Chem. 2000;275:18188-94 pubmed
    ..The availability of these mutants will make it possible to determine if there are direct, non-IGF-I-dependent effects of IGFBP-3 and -5 on cellular physiologic processes in cell types that secrete IGF-I. ..
  34. Twigg S, Kiefer M, Zapf J, Baxter R. Insulin-like growth factor-binding protein 5 complexes with the acid-labile subunit. Role of the carboxyl-terminal domain. J Biol Chem. 1998;273:28791-8 pubmed
    ..These findings are consistent with the basic carboxyl-terminal domain on IGFBP-5 being the principal site in IGFBP-5 that binds to ALS. ..
  35. Kim K, Seu Y, Baek S, Kim M, Kim K, Kim J, et al. Induction of cellular senescence by insulin-like growth factor binding protein-5 through a p53-dependent mechanism. Mol Biol Cell. 2007;18:4543-52 pubmed
    ..These results suggest that IGFBP-5 plays a role in the regulation of cellular senescence via a p53-dependent pathway and in aging-associated vascular diseases. ..
  36. Ewton D, Coolican S, Mohan S, Chernausek S, Florini J. Modulation of insulin-like growth factor actions in L6A1 myoblasts by insulin-like growth factor binding protein (IGFBP)-4 and IGFBP-5: a dual role for IGFBP-5. J Cell Physiol. 1998;177:47-57 pubmed
    ..IGFBP-5, however, is capable of eliciting a dual response, possibly due to its unique ability to associate with the cell membrane. ..
  37. Kuemmerle J, Zhou H. Insulin-like growth factor-binding protein-5 (IGFBP-5) stimulates growth and IGF-I secretion in human intestinal smooth muscle by Ras-dependent activation of p38 MAP kinase and Erk1/2 pathways. J Biol Chem. 2002;277:20563-71 pubmed
    ..A positive feedback mechanism therefore links IGFBP-5 and IGF-I secretion that reinforces their individual effects on growth. ..
  38. Walker G, MacLeod K, Williams A, Cameron D, Smyth J, Langdon S. Insulin-like growth factor binding proteins IGFBP3, IGFBP4, and IGFBP5 predict endocrine responsiveness in patients with ovarian cancer. Clin Cancer Res. 2007;13:1438-44 pubmed
    ..These results indicate that expression levels of certain IGFBP family members in ovarian cancers are estrogen regulated and can, thus, help identify patients who could benefit from endocrine therapy. ..
  39. Perks C, McCaig C, Clarke J, Clemmons D, Holly J. Effects of a non-IGF binding mutant of IGFBP-5 on cell death in human breast cancer cells. Biochem Biophys Res Commun. 2002;294:995-1000 pubmed
    ..In summary, all forms of IGFBP-5 modulated ceramide-induced apoptosis in Hs578T cells. In MCF-7 cells, IGF-I-induced survival could be facilitated by IGFBP-5, but also blocked by IGFBP-5 if association with IGFBP-5 was prevented. ..
  40. Zhao Y, Yin P, Bach L, Duan C. Several acidic amino acids in the N-domain of insulin-like growth factor-binding protein-5 are important for its transactivation activity. J Biol Chem. 2006;281:14184-91 pubmed
    ..Taken together, our results indicate that there are several conserved residues in the IGFBP-5 N-terminal region that are critical for transactivation and that IGFBP-2 and -3 also have strong transactivation activity in their N-domains. ..
  41. Kou K, Mittanck D, Fu C, Rotwein P. Structure and function of the mouse insulin-like growth factor binding protein 5 gene promoter. DNA Cell Biol. 1995;14:241-9 pubmed
    ..abstract truncated at 250 words) ..
  42. Ren H, Yin P, Duan C. IGFBP-5 regulates muscle cell differentiation by binding to IGF-II and switching on the IGF-II auto-regulation loop. J Cell Biol. 2008;182:979-91 pubmed publisher
    ..These findings suggest that IGFBP-5 promotes muscle cell differentiation by binding to and switching on the IGF-II auto-regulation loop. ..
  43. Xu Q, Yan B, Li S, Duan C. Fibronectin binds insulin-like growth factor-binding protein 5 and abolishes Its ligand-dependent action on cell migration. J Biol Chem. 2004;279:4269-77 pubmed
    ..These results suggest that FN and IGFBP-5 bind to each other, and this binding negatively regulates the ligand-dependent action of IGFBP-5 by triggering IGFBP-5 proteolysis. ..
  44. Miyatake T, Ueda Y, Nakashima R, Yoshino K, Kimura T, Murata T, et al. Down-regulation of insulin-like growth factor binding protein-5 (IGFBP-5): novel marker for cervical carcinogenesis. Int J Cancer. 2007;120:2068-77 pubmed
    ..001). This is the first study to show that down-regulation of IGFBP-5 protein correlates with cervical carcinogenesis and does so at a preneoplastic stage. ..
  45. Govoni K, Amaar Y, Kramer A, Winter E, Baylink D, Mohan S. Regulation of insulin-like growth factor binding protein-5, four and a half lim-2, and a disintegrin and metalloprotease-9 expression in osteoblasts. Growth Horm IGF Res. 2006;16:49-56 pubmed
    ..05). In conclusion, our findings are consistent with the hypothesis that FHL-2 and ADAM-9 are important modulators of IGFBP-5 actions and are, in part, regulated in a coordinated manner in bone. ..
  46. McCaig C, Perks C, Holly J. Signalling pathways involved in the direct effects of IGFBP-5 on breast epithelial cell attachment and survival. J Cell Biochem. 2002;84:784-94 pubmed
    ..These data suggest that IGFBP-5 promotes the attachment and survival of Hs578T cells by modulating the balance between ceramide and opposing survival signals. ..
  47. Tanno B, Cesi V, Vitali R, Sesti F, Giuffrida M, Mancini C, et al. Silencing of endogenous IGFBP-5 by micro RNA interference affects proliferation, apoptosis and differentiation of neuroblastoma cells. Cell Death Differ. 2005;12:213-23 pubmed
    ..Together, these data demonstrate the importance of IGFBP-5 for NB cell functions and suggest that IGFBP-5 might serve as a novel therapeutic target in NB. ..
  48. Yin P, Xu Q, Duan C. Paradoxical actions of endogenous and exogenous insulin-like growth factor-binding protein-5 revealed by RNA interference analysis. J Biol Chem. 2004;279:32660-6 pubmed
    ..These results indicate that endogenous and exogenous IGFBP-5 exhibits opposing biological actions on cell survival and underscore the necessity and utility of studying IGFBP functions through loss-of-function approaches. ..
  49. Johnson S, Dennis R, Barone G, Lamps L, Haun R. Differential expression of insulin-like growth factor binding protein-5 in pancreatic adenocarcinomas: identification using DNA microarray. Mol Carcinog. 2006;45:814-27 pubmed
    ..As a potential modulator of cell proliferation, the overexpression of IGFBP-5 may, therefore, play a significant role in the malignant transformation of normal pancreatic epithelial cells. ..
  50. Nam T, Busby W, Clemmons D. Insulin-like growth factor binding protein-5 binds to plasminogen activator inhibitor-I. Endocrinology. 1997;138:2972-8 pubmed
    ..PAI-1 binding partially protects IGFBP-5 from proteolysis, suggesting that it is one of the ECM components that is involved in mediating this effect. ..
  51. Cobb L, Salih D, Gonzalez I, Tripathi G, Carter E, Lovett F, et al. Partitioning of IGFBP-5 actions in myogenesis: IGF-independent anti-apoptotic function. J Cell Sci. 2004;117:1737-46 pubmed
    ..Our findings suggest that, by regulation of cell survival, IGFBP-5 has an autonomous role in the regulation of cell fate in development and in tumourigenesis. ..
  52. Nam T, Busby W, Rees C, Clemmons D. Thrombospondin and osteopontin bind to insulin-like growth factor (IGF)-binding protein-5 leading to an alteration in IGF-I-stimulated cell growth. Endocrinology. 2000;141:1100-6 pubmed
    ..These interactions may be important for concentrating intact IGFBP-5 in extracellular matrix and for modulating the cooperative interaction between the IGF-I receptor and integrin receptor signaling pathways. ..
  53. Clemmons D, Busby W, Garmong A, Schultz D, Howell D, Altman R, et al. Inhibition of insulin-like growth factor binding protein 5 proteolysis in articular cartilage and joint fluid results in enhanced concentrations of insulin-like growth factor 1 and is associated with improved osteoarthritis. Arthritis Rheum. 2002;46:694-703 pubmed
    ..This increase in concentrations of intact IGFBP-3 and IGFBP-5 leads to an increase in IGF-1 which is associated with an improvement in joint architecture during the development of OA. ..