Shainer Reut, Kram Vardit, Kilts Tina M, Li Li, Doyle Andrew D, Shainer Inbal, Martin Daniel, Simon Carl G, Zeng-Brouwers Jinyang, Schaefer Liliana, Young Marian F
Molecular Biology of Bones and Teeth Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, United States.
NIDCR Imaging Core, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, United States.
Front Physiol. 2023 Feb 16;14:1119368. doi: 10.3389/fphys.2023.1119368. eCollection 2023.
Endochondral bone development and regeneration relies on activation and proliferation of periosteum derived-cells (PDCs). Biglycan (Bgn), a small proteoglycan found in extracellular matrix, is known to be expressed in bone and cartilage, however little is known about its influence during bone development. Here we link biglycan with osteoblast maturation starting during embryonic development that later affects bone integrity and strength. Biglycan gene deletion reduced the inflammatory response after fracture, leading to impaired periosteal expansion and callus formation. Using a novel 3D scaffold with PDCs, we found that biglycan could be important for the cartilage phase preceding bone formation. The absence of biglycan led to accelerated bone development with high levels of osteopontin, which appeared to be detrimental to the structural integrity of the bone. Collectively, our study identifies biglycan as an influencing factor in PDCs activation during bone development and bone regeneration after fracture.
软骨内骨发育和再生依赖于骨膜衍生细胞（PDCs）的激活和增殖。双糖链蛋白聚糖（Bgn）是一种存在于细胞外基质中的小蛋白聚糖，已知在骨骼和软骨中表达，然而其在骨骼发育过程中的影响却知之甚少。在这里，我们将双糖链蛋白聚糖与胚胎发育期间开始的成骨细胞成熟联系起来，这随后会影响骨骼的完整性和强度。双糖链蛋白聚糖基因缺失减少了骨折后的炎症反应，导致骨膜扩张和骨痂形成受损。使用一种带有PDCs的新型3D支架，我们发现双糖链蛋白聚糖对于骨形成之前的软骨阶段可能很重要。双糖链蛋白聚糖的缺失导致骨桥蛋白水平升高，从而加速了骨骼发育，这似乎对骨骼的结构完整性有害。总的来说，我们的研究确定双糖链蛋白聚糖是骨骼发育和骨折后骨再生过程中影响PDCs激活的一个因素。
