Biglycan regulates bone development and regeneration

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 Bgn with osteoblast maturation starting during embryonic development that with aging affects bone integrity and strength. Bgn gene deletion reduced the inflammatory response after fracture, leading to impaired periostal expansion and callus formation. Using novel 3D scaffold and analyzing newborn bones, we found that Bgn is required for the cartilage-bone transition of PDCs during endochondral bone development. The absence of Bgn 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 Bgn as an important factor in PDCs activation during bone development and bone regeneration after fracture. In this study, we isolated cells from WT and Bgn KO embryos (E16.5) and newborn (P-3) bones Femurs from 6-7 week-old WT or Bgn KO male mice were fractured and collected for bulk RNAseq 3 days after fracture. For each mouse one femur was fractured and the second femur served as the control unfractured bone. contributor: NIDCD/NIDCR Genomics and Computational Biology Core软骨内骨发育与骨再生依赖于骨膜来源细胞（periosteum derived-cells，PDCs）的激活与增殖。饰胶蛋白聚糖（Biglycan，Bgn）是一类存在于细胞外基质（extracellular matrix）中的小分子蛋白聚糖，已知其在骨与软骨组织中表达，但目前对其在骨发育过程中的调控作用仍知之甚少。本研究将饰胶蛋白聚糖与胚胎发育阶段起始的成骨细胞成熟过程相关联，而该过程随衰老会影响骨组织的完整性与力学强度。敲除Bgn基因可减轻骨折后的炎症反应，但会损伤骨膜扩张与骨痂形成过程。本研究借助新型三维支架并分析新生骨组织，发现软骨内骨发育过程中，骨膜来源细胞（PDCs）的软骨-骨转化依赖于饰胶蛋白聚糖的存在。缺失饰胶蛋白聚糖会加速骨发育进程，同时伴随骨桥蛋白水平升高，该表型似乎对骨组织的结构完整性存在不利影响。综上，本研究证实饰胶蛋白聚糖是骨发育过程中骨膜来源细胞激活，以及骨折后骨再生的关键调控因子。 本研究中，我们分别从野生型（wild type，WT）与Bgn基因敲除（knock out，KO）胚胎（E16.5）及新生（P3）小鼠的骨组织中分离细胞；并对6~7周龄的野生型或Bgn基因敲除雄性小鼠的股骨进行骨折造模，于造模后3天收集样本开展批量RNA测序（bulk RNAseq）。每只小鼠的一根股骨用于骨折造模，另一根股骨作为未骨折对照样本。 数据贡献者：美国国家耳聋与其他交流障碍研究所/国家口腔与颅面研究所（NIDCD/NIDCR）基因组学与计算生物学核心实验室。