A Potential Participant in Type 2 Diabetes Bone Fragility: TIMP-1 at Sites of Osteocyte Lacunar-Canalicular System

Overview

Journal Diabetes Metab Syndr Obes

Publisher Dove Medical Press

Specialty Endocrinology

Date 2022 Jan 7

PMID 34992398

Citations 3

Authors

Qilin Pei

Jun Li

Pengfei Zhou

Jun Zhang

Peng Huang

Jingchuan Fan

Zhen Zou

Xi Li

Bin Wang

Affiliations

Soon will be listed here.

Abstract

Type 2 diabetes mellitus (T2DM) is associated with an increased risk of bone fracture, but the bone mineral density (BMD) is typically normal or higher in such patients. Because the fracture risk is independent of reduced BMD, bone fragility in T2DM may be partially due to poor bone quality. The mechanisms triggering bone quality abnormalities in T2DM are complex, and include the accumulation of advanced glycation end-products, the increased inflammation, and low bone turnover. Matrix metalloproteinases (MMPs) in bone can hydrolyze the bone matrix. Tissue inhibitors of MMPs (TIMPs) can inhibit the activity of MMPs. Both MMPs and TIMPs participate in mediating bone quality. Among all types of TIMPs, TIMP-1 is mostly reportedly increased in the serum of T2DM patients. Because osteocytes can express TIMP-1, and osteocyte pericellular matrix influences bone quality partially regulated by perilacunar/canalicular remodeling, we hypothesized that TIMP-1 at sites of osteocyte lacunar-canalicular system is involved in T2DM bone fragility.

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References

Inoue K, Mikuni-Takagaki Y, Oikawa K, Itoh T, Inada M, Noguchi T . A crucial role for matrix metalloproteinase 2 in osteocytic canalicular formation and bone metabolism. J Biol Chem. 2006; 281(44):33814-24. DOI: 10.1074/jbc.M607290200. View

Kerckhofs G, Durand M, Vangoitsenhoven R, Marin C, Van der Schueren B, Carmeliet G . Changes in bone macro- and microstructure in diabetic obese mice revealed by high resolution microfocus X-ray computed tomography. Sci Rep. 2016; 6:35517. PMC: 5069481. DOI: 10.1038/srep35517. View

Wang M, Sampson E, Jin H, Li J, Ke Q, Im H . MMP13 is a critical target gene during the progression of osteoarthritis. Arthritis Res Ther. 2013; 15(1):R5. PMC: 3672752. DOI: 10.1186/ar4133. View

Villarino M, Sanchez L, Bozal C, Ubios A . Influence of short-term diabetes on osteocytic lacunae of alveolar bone. A histomorphometric study. Acta Odontol Latinoam. 2006; 19(1):23-8. View

Bonewald L . The amazing osteocyte. J Bone Miner Res. 2011; 26(2):229-38. PMC: 3179345. DOI: 10.1002/jbmr.320. View

Ay B, Parolia K, Liddell R, Qiu Y, Grasselli G, Cooper D . Hyperglycemia compromises Rat Cortical Bone by Increasing Osteocyte Lacunar Density and Decreasing Vascular Canal Volume. Commun Biol. 2020; 3(1):20. PMC: 6952406. DOI: 10.1038/s42003-019-0747-1. View

Wang B, Zhou X, Price C, Li W, Pan J, Wang L . Quantifying load-induced solute transport and solute-matrix interaction within the osteocyte lacunar-canalicular system. J Bone Miner Res. 2012; 28(5):1075-86. PMC: 3593787. DOI: 10.1002/jbmr.1804. View

Geoffroy V, Marty-Morieux C, Le Goupil N, Clement-Lacroix P, Terraz C, Frain M . In vivo inhibition of osteoblastic metalloproteinases leads to increased trabecular bone mass. J Bone Miner Res. 2004; 19(5):811-22. DOI: 10.1359/JBMR.040119. View

Hatori K, Sasano Y, Takahashi I, Kamakura S, Kagayama M, Sasaki K . Osteoblasts and osteocytes express MMP2 and -8 and TIMP1, -2, and -3 along with extracellular matrix molecules during appositional bone formation. Anat Rec A Discov Mol Cell Evol Biol. 2004; 277(2):262-71. DOI: 10.1002/ar.a.20007. View

10.

van Tol A, Schemenz V, Wagermaier W, Roschger A, Razi H, Vitienes I . The mechanoresponse of bone is closely related to the osteocyte lacunocanalicular network architecture. Proc Natl Acad Sci U S A. 2020; 117(51):32251-32259. PMC: 7768754. DOI: 10.1073/pnas.2011504117. View

11.

Paiva K, Granjeiro J . Matrix Metalloproteinases in Bone Resorption, Remodeling, and Repair. Prog Mol Biol Transl Sci. 2017; 148:203-303. DOI: 10.1016/bs.pmbts.2017.05.001. View

12.

Mazur C, Woo J, Yee C, Fields A, Acevedo C, Bailey K . Osteocyte dysfunction promotes osteoarthritis through MMP13-dependent suppression of subchondral bone homeostasis. Bone Res. 2019; 7:34. PMC: 6828661. DOI: 10.1038/s41413-019-0070-y. View

13.

Janghorbani M, van Dam R, Willett W, Hu F . Systematic review of type 1 and type 2 diabetes mellitus and risk of fracture. Am J Epidemiol. 2007; 166(5):495-505. DOI: 10.1093/aje/kwm106. View

14.

Schwartz A, Vittinghoff E, Bauer D, Hillier T, Strotmeyer E, Ensrud K . Association of BMD and FRAX score with risk of fracture in older adults with type 2 diabetes. JAMA. 2011; 305(21):2184-92. PMC: 3287389. DOI: 10.1001/jama.2011.715. View

15.

Baker A, Edwards D, Murphy G . Metalloproteinase inhibitors: biological actions and therapeutic opportunities. J Cell Sci. 2002; 115(Pt 19):3719-27. DOI: 10.1242/jcs.00063. View

16.

Tang S, Herber R, Ho S, Alliston T . Matrix metalloproteinase-13 is required for osteocytic perilacunar remodeling and maintains bone fracture resistance. J Bone Miner Res. 2012; 27(9):1936-50. PMC: 3415585. DOI: 10.1002/jbmr.1646. View

17.

Lai X, Price C, Modla S, Thompson W, Caplan J, Kirn-Safran C . The dependences of osteocyte network on bone compartment, age, and disease. Bone Res. 2015; 3. PMC: 4511381. DOI: 10.1038/boneres.2015.9. View

18.

Eckhardt B, Rowsey J, Thicke B, Fraser D, OGrady K, Bondar O . Accelerated osteocyte senescence and skeletal fragility in mice with type 2 diabetes. JCI Insight. 2020; 5(9). PMC: 7253018. DOI: 10.1172/jci.insight.135236. View

19.

Prideaux M, Staines K, Jones E, Riley G, Pitsillides A, Farquharson C . MMP and TIMP temporal gene expression during osteocytogenesis. Gene Expr Patterns. 2015; 18(1-2):29-36. DOI: 10.1016/j.gep.2015.04.004. View

20.

Dallas S, Prideaux M, Bonewald L . The osteocyte: an endocrine cell ... and more. Endocr Rev. 2013; 34(5):658-90. PMC: 3785641. DOI: 10.1210/er.2012-1026. View