Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 May;45(5):1045-1057.
doi: 10.1007/s40618-022-01740-7. Epub 2022 Jan 12.

Direct effects of octreotide on osteoblast cell proliferation and function

E Vitali  1   2 , E Palagano  3 , M L Schiavone  4 , G Mantovani  5   6 , C Sobacchi  4   7 , G Mazziotti  8   9 , A Lania  1   10
Affiliations

Direct effects of octreotide on osteoblast cell proliferation and function

E Vitali et al. J Endocrinol Invest. 2022 May.

Abstract

Purpose: Octreotide (OCT) is a first-generation somatostatin analog (SSA) used in the treatment of acromegaly and neuroendocrine tumors (NETs). In both diseases, OCT interacts with somatostatin receptors 2 and 5 (SSTR2 and SSTR5), inhibiting hormone hypersecretion and cell proliferation. Skeletal health is an important clinical concern in acromegaly and NETs, since acromegalic osteopathy and NET bone metastasis occur in a remarkable number of patients. While OCT's effect on NET and pituitary cells has been extensively investigated, its direct action on bone cells remains unknown.

Methods: Here, we investigated OCT direct effects on cell proliferation, differentiation, mineralization, and chemoattractant capacity of murine primary osteoblasts and osteoblast cell line MC3T3-E1.

Results: OCT inhibited osteoblasts and MC3T3-E1 cell proliferation (- 30 ± 16%, and - 22 ± 4%, both p < 0.05 vs control) and increased MC3T3-E1 cell apoptosis (+ 76 ± 32%, p < 0.05 vs control). The anti-proliferative action of OCT was mediated by SSTR2 and SSTR5 in MC3T3-E1, while its pro-apoptotic effect was abrogated in SSTR2-silenced cells. The analysis of genes related to the early and late phases of osteoblast differentiation showed that OCT did not affect Alp, Runx2, Bglap, Spp1, and Sost levels in MC3T3-E1 cells. Similarly, OCT did not affect ALP activity, mineralization, and osteoclastogenic induction. Finally, Vegfa expression decreased in OCT-treated MC3T3-E1 cells and OCT inhibited pancreatic NET cell migration toward the osteoblast-conditioned medium.

Conclusion: This study provides the first evidence of the direct action of OCT on osteoblasts which may have clinically relevant implications for the management of skeletal health in subjects with acromegaly and metastatic NETs.

Keywords: Acromegaly; Bone; Neuroendocrine tumors; Octreotide; Osteoblast; Somatostatin.

PubMed Disclaimer

References

    1. Taboada GF, Luque RM, Neto LV et al (2008) Quantitative analysis of somatostatin receptor subtypes (1–5) gene expression levels in somatotropinomas and correlation to in vivo hormonal and tumor volume responses to treatment with octreotide LAR. Eur J Endocrinol 158:295–303. https://doi.org/10.1530/EJE-07-0562 - DOI - PubMed
    1. Körner M, Eltschinger V, Waser B et al (2005) Value of immunohistochemistry for somatostatin receptor subtype sst2A in cancer tissues: lessons from the comparison of anti-sst2A antibodies with somatostatin receptor autoradiography. Am J Surg Pathol 29:1642–1651. https://doi.org/10.1097/01.pas.0000174013.14569.90 - DOI - PubMed
    1. De Marinis L, Bianchi A, Mazziotti G et al (2008) The long-term cardiovascular outcome of different GH-lowering treatments in acromegaly. Pituitary 11:13–20. https://doi.org/10.1007/s11102-007-0062-6 - DOI - PubMed
    1. Mazziotti G, Floriani I, Bonadonna S et al (2009) Effects of somatostatin analogs on glucose homeostasis: a metaanalysis of acromegaly studies. J Clin Endocrinol Metab 94:1500–1508. https://doi.org/10.1210/jc.2008-2332 - DOI - PubMed
    1. Giustina A, Mazziotti G, Canalis E (2008) Growth hormone, insulin-like growth factors, and the skeleton. Endocr Rev 29:535–559. https://doi.org/10.1210/er.2007-0036 - DOI - PubMed - PMC

Grants and funding

LinkOut - more resources