Dong Wei, Yang Chang, Guo Donghua, Jia Meie, Wang Yan, Wang Jiawei
State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan 430079, China.
State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan 430079, China.
Bone. 2025 Mar;192:117385. doi: 10.1016/j.bone.2024.117385. Epub 2024 Dec 26.
Endochondral ossification (EO) is a pivotal process during fracture healing and traumatic heterotopic ossification (HO), involving the cartilaginous matrix synthesis and mineralization. Unlike the extracellular matrix, the hyaluronan (HA)-rich pericellular matrix (PCM) directly envelops chondrocytes, serving as the frontline for extracellular signal reception and undergoing dynamic remodeling. Pentraxin 3 (PTX3), a secreted glycoprotein, facilitates HA matrix assembly and remodeling. However, it remains unclear whether PTX3 affects EO by regulating HA-rich PCM assembly of chondrocytes, thereby impacting fracture healing and traumatic HO. This study demonstrates that PTX3 deficiency impairs fracture healing and inhibits traumatic HO, but dose not affect growth plate development in mice. PTX3 expression is up-regulated during chondrocyte matrix synthesis and maturation and is localized in the HA-rich PCM. PTX3 promotes the assembly of HA-rich PCM in a serum- and TSG6-dependent manner, fostering CD44 receptor clustering, activating the FAK/AKT signaling pathway, and promoting chondrocyte matrix synthesis and maturation. Local injection of PTX3/TSG6 matrix protein mixture effectively promotes fracture healing in mice. In conclusion, PTX3-assembled HA-rich PCM promotes chondrocyte matrix synthesis and maturation via CD44/FAK/AKT signaling. This mechanism facilitates EO during fracture healing and traumatic HO in mice.
软骨内成骨（EO）是骨折愈合和创伤性异位骨化（HO）过程中的关键环节，涉及软骨基质的合成与矿化。与细胞外基质不同，富含透明质酸（HA）的细胞周基质（PCM）直接包裹软骨细胞，作为细胞外信号接收的前沿并经历动态重塑。五聚体3（PTX3）是一种分泌型糖蛋白，可促进HA基质的组装和重塑。然而，PTX3是否通过调节软骨细胞富含HA的PCM组装来影响EO，进而影响骨折愈合和创伤性HO，仍不清楚。本研究表明，PTX3缺乏会损害骨折愈合并抑制创伤性HO，但不影响小鼠生长板发育。PTX3在软骨细胞基质合成和成熟过程中表达上调，并定位于富含HA的PCM中。PTX3以血清和TSG6依赖的方式促进富含HA的PCM组装，促进CD44受体聚集，激活FAK/AKT信号通路，并促进软骨细胞基质合成和成熟。局部注射PTX3/TSG6基质蛋白混合物可有效促进小鼠骨折愈合。总之，PTX3组装的富含HA的PCM通过CD44/FAK/AKT信号促进软骨细胞基质合成和成熟。这一机制促进了小鼠骨折愈合和创伤性HO过程中的EO。
