Matthew J. Silva, PhD

Professor
Orthopaedic Surgery
Associate Professor
Biomedical Engineering

Molecular Cell Biology Program
Human and Statistical Genetics Program

Research Abstract:

Our focus is bone. Bone is a living material filled with cells that, when healthy, allow the skeleton to adapt to its physical loading environment, maintain itself over 70+ years of use, and self-repair after injury. Despite these remarkable qualities, with advancing age the skeleton’s abilities to respond to physical stimuli and to self-repair are diminished.

Our lab focuses on two main questions. 1) How does mechanical loading stimulate bone formation? Mechanical (physical) loading is a powerful stimulus to increase bone formation, whereby new layers of bone tissue are added onto existing bone surfaces, resulting in increased bone mass and strength. But the mechanisms for how the skeleton converts a mechanical stimulus to increased bone formation are not fully understood. We are studying the origin of the bone-forming cells (osteoblasts) and the role of the Wnt signaling pathway in loading-induced bone formation. We are also studying how aging affects each of these processes. The second question is: 2) How do bones heal after injury? The skeleton has a tremendous capacity for self-repair after stress fracture and full fracture. But under some conditions the native ability for repair is inadequate and a surgical intervention is required. Stress fractures heal by a combination of internal remodeling and external woven bone formation, also known as periosteal hard callus. Full fractures heal by these processes plus the formation of a temporary cartilage (soft) callus that is eventually replaced by bone. We are studying the role of bone cells in coordinating the complex fracture healing response, which also involves immune cells and the formation of new blood vessels (angiogenesis).

Selected Publications:

Link to Pubmed: https://www.ncbi.nlm.nih.gov/myncbi/1lYOzcTNQbU5p/bibliography/public/
Link to Google Scholar: https://scholar.google.com/citations?hl=en&user=h5LAOvEAAAAJ

McKenzie JA, Galbreath IM, Coello AF, Hixon KR, Silva MJ. VEGFA from osteoblasts is not required for lamellar bone formation following tibial loading. Bone. 2022 Oct;163:116502. doi: 10.1016/j.bone.2022.116502. Epub 2022 Jul 21. PubMed PMID: 35872107; PubMed Central PMCID: PMC9624127.

Lawson LY, Migotsky N, Chermside-Scabbo CJ, Shuster JT, Joeng KS, Civitelli R, Lee B, Silva MJ. Loading-induced bone formation is mediated by Wnt1 induction in osteoblast-lineage cells. FASEB J. 2022 Sep;36(9):e22502. doi: 10.1096/fj.202200591R. PubMed PMID: 35969160; PubMed Central PMCID: PMC9430819.

Hixon KR, Katz DB, McKenzie JA, Miller AN, Guilak F, Silva MJ. Cryogel Scaffold-Mediated Delivery of Adipose-Derived Stem Cells Promotes Healing in Murine Model of Atrophic Non-Union. Front Bioeng Biotechnol. 2022;10:851904. doi: 10.3389/fbioe.2022.851904. eCollection 2022. PubMed PMID: 35600896; PubMed Central PMCID: PMC9117654.

Sun K, Wang C, Xiao J, Brodt MD, Yuan L, Yang T, Alippe Y, Hu H, Hao D, Abu-Amer Y, Silva MJ, Shen J, Mbalaviele G. Fracture healing is delayed in the absence of gasdermin-interleukin-1 signaling. Elife. 2022 Mar 4;11. doi: 10.7554/eLife.75753. PubMed PMID: 35244027; PubMed Central PMCID: PMC8923664.

Harris TL, Silva MJ. Dmp1 Lineage Cells Contribute Significantly to Periosteal Lamellar Bone Formation Induced by Mechanical Loading But Are Depleted from the Bone Surface During Rapid Bone Formation. JBMR Plus. 2022 Mar;6(3):e10593. doi: 10.1002/jbm4.10593. eCollection 2022 Mar. PubMed PMID: 35309865; PubMed Central PMCID: PMC8914163.

Yan M, Duan X, Cai L, Zhang W, Silva MJ, Brophy RH, Rai MF. KIF26B Silencing Prevents Osseous Transdifferentiation of Progenitor/Stem Cells and Attenuates Ectopic Calcification in a Murine Model. J Bone Miner Res. 2022 Feb;37(2):349-368. doi: 10.1002/jbmr.4473. Epub 2021 Dec 14. PubMed PMID: 34787331.

Lawson LY, Brodt MD, Migotsky N, Chermside-Scabbo CJ, Palaniappan R, Silva MJ. Osteoblast-Specific Wnt Secretion Is Required for Skeletal Homeostasis and Loading-Induced Bone Formation in Adult Mice. J Bone Miner Res. 2022 Jan;37(1):108-120. doi: 10.1002/jbmr.4445. Epub 2021 Oct 11. PubMed PMID: 34542191; PubMed Central PMCID: PMC8770559.

Hixon KR, McKenzie JA, Sykes DAW, Yoneda S, Hensley A, Buettmann EG, Zheng H, Skouteris D, McAlinden A, Miller AN, Silva MJ. Ablation of Proliferating Osteoblast Lineage Cells After Fracture Leads to Atrophic Nonunion in a Mouse Model. J Bone Miner Res. 2021 Nov;36(11):2243-2257. doi: 10.1002/jbmr.4424. Epub 2021 Sep 7. PubMed PMID: 34405443; PubMed Central PMCID: PMC8719642.

Harris TL, Silva MJ. Gene expression of intracortical bone demonstrates loading-induced increases in Wnt1 and Ngf and inhibition of bone remodeling processes. Bone. 2021 Sep;150:116019. doi: 10.1016/j.bone.2021.116019. Epub 2021 May 21. PubMed PMID: 34023542; PubMed Central PMCID: PMC8408835.

Hu P, McKenzie JA, Buettmann EG, Migotsky N, Gardner MJ, Silva MJ. Type 1 diabetic Akita mice have low bone mass and impaired fracture healing. Bone. 2021 Jun;147:115906. doi: 10.1016/j.bone.2021.115906. Epub 2021 Mar 2. PubMed PMID: 33662611; PubMed Central PMCID: PMC8546917.

Berke IM, Jain E, Yavuz B, McGrath T, Chen L, Silva MJ, Mbalaviele G, Guilak F, Kaplan DL, Setton LA. NF-κB-mediated effects on behavior and cartilage pathology in a non-invasive loading model of post-traumatic osteoarthritis. Osteoarthritis Cartilage. 2021 Feb;29(2):248-256. doi: 10.1016/j.joca.2020.10.008. Epub 2020 Nov 24. PubMed PMID: 33246158; PubMed Central PMCID: PMC8023431.

Coates BA, McKenzie JA, Yoneda S, Silva MJ. Interleukin-6 (IL-6) deficiency enhances intramembranous osteogenesis following stress fracture in mice. Bone. 2021 Feb;143:115737. doi: 10.1016/j.bone.2020.115737. Epub 2020 Nov 10. PubMed PMID: 33181349; PubMed Central PMCID: PMC8408837.

Pickering E, Silva MJ, Delisser P, Brodt MD, Gu Y, Pivonka P. Estimation of load conditions and strain distribution for in vivo murine tibia compression loading using experimentally informed finite element models. J Biomech. 2021 Jan 22;115:110140. doi: 10.1016/j.jbiomech.2020.110140. Epub 2020 Dec 13. PubMed PMID: 33348259; PubMed Central PMCID: PMC7856106.

Kim Y, Brodt MD, Tang SY, Silva MJ. MicroCT for Scanning and Analysis of Mouse Bones. Methods Mol Biol. 2021;2230:169-198. doi: 10.1007/978-1-0716-1028-2_11. PubMed PMID: 33197015; PubMed Central PMCID: PMC8409170.

Piccoli A, Cannata F, Strollo R, Pedone C, Leanza G, Russo F, Greto V, Isgrò C, Quattrocchi CC, Massaroni C, Silvestri S, Vadalà G, Bisogno T, Denaro V, Pozzilli P, Tang SY, Silva MJ, Conte C, Papalia R, Maccarrone M, Napoli N. Sclerostin Regulation, Microarchitecture, and Advanced Glycation End-Products in the Bone of Elderly Women With Type 2 Diabetes. J Bone Miner Res. 2020 Dec;35(12):2415-2422. doi: 10.1002/jbmr.4153. Epub 2020 Oct 2. PubMed PMID: 32777114; PubMed Central PMCID: PMC8143610.

Zou W, Rohatgi N, Brestoff JR, Li Y, Barve RA, Tycksen E, Kim Y, Silva MJ, Teitelbaum SL. Ablation of Fat Cells in Adult Mice Induces Massive Bone Gain. Cell Metab. 2020 Nov 3;32(5):801-813.e6. doi: 10.1016/j.cmet.2020.09.011. Epub 2020 Oct 6. PubMed PMID: 33027637; PubMed Central PMCID: PMC7642038.

Rai MF, Sandell LJ, Barrack TN, Cai L, Tycksen ED, Tang SY, Silva MJ, Barrack RL. A Microarray Study of Articular Cartilage in Relation to Obesity and Severity of Knee Osteoarthritis. Cartilage. 2020 Oct;11(4):458-472. doi: 10.1177/1947603518796122. Epub 2018 Sep 3. PubMed PMID: 30173558; PubMed Central PMCID: PMC7488940.

Chermside-Scabbo CJ, Harris TL, Brodt MD, Braenne I, Zhang B, Farber CR, Silva MJ. Old Mice Have Less Transcriptional Activation But Similar Periosteal Cell Proliferation Compared to Young-Adult Mice in Response to in vivo Mechanical Loading. J Bone Miner Res. 2020 Sep;35(9):1751-1764. doi: 10.1002/jbmr.4031. Epub 2020 Jun 1. PubMed PMID: 32311160; PubMed Central PMCID: PMC7486279.

Zannit HM, Brodt MD, Silva MJ. Proliferating osteoblasts are necessary for maximal bone anabolic response to loading in mice. FASEB J. 2020 Sep;34(9):12739-12750. doi: 10.1096/fj.202000614R. Epub 2020 Aug 3. PubMed PMID: 32744762; PubMed Central PMCID: PMC7833806.

Coates BA, Silva MJ. An animal trial to study damage and repair in ovariectomized rabbits. J Biomech. 2020 Jul 17;108:109866. doi: 10.1016/j.jbiomech.2020.109866. Epub 2020 Jun 20. PubMed PMID: 32635993.

Morrell AE, Robinson ST, Silva MJ, Guo XE. Mechanosensitive Ca2+ signaling and coordination is diminished in osteocytes of aged mice during ex vivo tibial loading. Connect Tissue Res. 2020 May-Jul;61(3-4):389-398. doi: 10.1080/03008207.2020.1712377. Epub 2020 Jan 13. PubMed PMID: 31931640; PubMed Central PMCID: PMC7785095.

Last Updated: 11/8/2022 11:28:00 AM

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