IGF-1 C.258 A > G Synonymous Mutation Ameliorates Senile Osteoporosis

Overview

Journal Commun Biol

Specialty Biology

Date 2024 Dec 20

PMID 39702559

Authors

Zhaoguo Wang

Dayou Dai

Siyao Wang

Libo Zhang

Yi Li

Xunming Zhang

Yunyun Cheng

Linlin Hao

Affiliations

Soon will be listed here.

Abstract

Senile osteoporosis (SOP) is a multifactorial, age-related progressive phenomenon with a considerable morbidity and mortality. IGF-1 is an important regulator of bone reconstruction and metabolism throughout life. Nevertheless, our previous study unexpectedly found there is no change in the peak bone mass with a altered IGF-1 gene expression leaded by IGF-1 c.258 A > G synonymous mutation. Considering its involvement in the cellular senescence, we suspected c.258 A > G may participate in SOP. Therefore, the effect of IGF-1 c.258 A > G on SOP was firstly detected, the changes of bone formation and bone resorption index in SOP mice with two genotypes indicated it improved SOP. Then, the in vitro study confirmed the mutation ameliorates SOP by promoting the growth and development of senescent osteoblasts. At last, co-culture of osteoblast and osteoclast further verified the mutation prevents SOP by increasing the bone formation capacity of senescent osteoblasts. Collectively, this study illuminated the role of IGF-1 c.258 A > G in ameliorating SOP.

Citing Articles

IGF-1 c.258 A > G synonymous mutation ameliorates senile osteoporosis.

Wang Z, Dai D, Wang S, Zhang L, Li Y, Zhang X Commun Biol. 2024; 7(1):1675.

PMID: 39702559 PMC: 11659520. DOI: 10.1038/s42003-024-07369-x.

References

Kao C, Hsu H, Chen Y, Tu M, Chuang S, Su S . The Decisive Case-Control Study Elaborates the Null Association between rs226794 and Osteoarthritis in Asians: A Case-Control Study and Meta-Analysis. Genes (Basel). 2021; 12(12). PMC: 8701278. DOI: 10.3390/genes12121916. View

Wang J, Zhu Q, Cao D, Peng Q, Zhang X, Li C . Bone marrow-derived IGF-1 orchestrates maintenance and regeneration of the adult skeleton. Proc Natl Acad Sci U S A. 2022; 120(1):e2203779120. PMC: 9910602. DOI: 10.1073/pnas.2203779120. View

Govoni K, Baylink D, Mohan S . The multi-functional role of insulin-like growth factor binding proteins in bone. Pediatr Nephrol. 2004; 20(3):261-8. PMC: 2923924. DOI: 10.1007/s00467-004-1658-y. View

Nishimura R, Hata K, Kida J . [Regulation of osteoblasts and chondrocytes by Wnt signaling.]. Clin Calcium. 2019; 29(3):299-307. DOI: 10.20837/4201903299. View

Wang Z, Dai D, Wang S, Zhang L, Li Y, Zhang X . IGF-1 c.258 A > G synonymous mutation ameliorates senile osteoporosis. Commun Biol. 2024; 7(1):1675. PMC: 11659520. DOI: 10.1038/s42003-024-07369-x. View

Liu Y, Zhao D, Wang W, Wang B, Zhang Y, Li Z . Association of the g.27563G>A osteoprotegerin genetic polymorphism with bone mineral density in Chinese women. Genet Mol Res. 2014; 13(2):3560-6. DOI: 10.4238/2014.February.14.9. View

Ilyas Z, Camacho P . Rare adverse effects of bisphosphonate therapy. Curr Opin Endocrinol Diabetes Obes. 2019; 26(6):335-338. DOI: 10.1097/MED.0000000000000501. View

Matsushita M, Tsuboyama T, Kasai R, Okumura H, Yamamuro T, Higuchi K . Age-related changes in bone mass in the senescence-accelerated mouse (SAM). SAM-R/3 and SAM-P/6 as new murine models for senile osteoporosis. Am J Pathol. 1986; 125(2):276-83. PMC: 1888250. View

Cheng Y, Liu S, Wang G, Wei W, Huang S, Yang R . Porcine IGF1 synonymous mutation alter gene expression and protein binding affinity with IGF1R. Int J Biol Macromol. 2018; 116:23-30. DOI: 10.1016/j.ijbiomac.2018.05.022. View

10.

Zhong Y, Li J, Luo J, Chen F . Advances in Bone Turnover Markers (PINP and CTX) in Optimizing Anti-resorptive and Anabolic Therapies Against Osteoporosis. Discov Med. 2022; 32(167):149-154. View

11.

Rico-Llanos G, Becerra J, Visser R . Insulin-like growth factor-1 (IGF-1) enhances the osteogenic activity of bone morphogenetic protein-6 (BMP-6) in vitro and in vivo, and together have a stronger osteogenic effect than when IGF-1 is combined with BMP-2. J Biomed Mater Res A. 2017; 105(7):1867-1875. DOI: 10.1002/jbm.a.36051. View

12.

Scicchitano B, Rizzuto E, Musaro A . Counteracting muscle wasting in aging and neuromuscular diseases: the critical role of IGF-1. Aging (Albany NY). 2010; 1(5):451-7. PMC: 2806025. DOI: 10.18632/aging.100050. View

13.

Hurley M, Abreu C, Hakeda Y . Basic fibroblast growth factor regulates IGF-I binding proteins in the clonal osteoblastic cell line MC3T3-E1. J Bone Miner Res. 1995; 10(2):222-30. DOI: 10.1002/jbmr.5650100208. View

14.

Coughlan T, Dockery F . Osteoporosis and fracture risk in older people. Clin Med (Lond). 2014; 14(2):187-91. PMC: 4953292. DOI: 10.7861/clinmedicine.14-2-187. View

15.

Saferding V, Hofmann M, Brunner J, Niederreiter B, Timmen M, Magilnick N . microRNA-146a controls age-related bone loss. Aging Cell. 2020; 19(11):e13244. PMC: 7681058. DOI: 10.1111/acel.13244. View

16.

Wang Y, Deng P, Liu Y, Wu Y, Chen Y, Guo Y . Alpha-ketoglutarate ameliorates age-related osteoporosis via regulating histone methylations. Nat Commun. 2020; 11(1):5596. PMC: 7645772. DOI: 10.1038/s41467-020-19360-1. View

17.

Giustina A, Mazziotti G, Canalis E . Growth hormone, insulin-like growth factors, and the skeleton. Endocr Rev. 2008; 29(5):535-59. PMC: 2726838. DOI: 10.1210/er.2007-0036. View

18.

Crane J, Cao X . Function of matrix IGF-1 in coupling bone resorption and formation. J Mol Med (Berl). 2013; 92(2):107-15. PMC: 3946714. DOI: 10.1007/s00109-013-1084-3. View

19.

Hosoi T . Genetic aspects of osteoporosis. J Bone Miner Metab. 2010; 28(6):601-7. DOI: 10.1007/s00774-010-0217-9. View

20.

Chen C, Tseng K, Lai Y, Chen Y, Lin F, Lin S . Overexpression of Insulin-Like Growth Factor 1 Enhanced the Osteogenic Capability of Aging Bone Marrow Mesenchymal Stem Cells. Theranostics. 2017; 7(6):1598-1611. PMC: 5436515. DOI: 10.7150/thno.16637. View