A research team from Wuhan University identified CAR3 as a key osteoblast protein that promotes collagen mineralization, bone formation, and skeletal regeneration, according to findings published on June 26.
The study, led by Dr. Fangfang Song and Professor Yufeng Zhang, investigated the function of carbonic anhydrase III (CAR3) in skeletal development using genetically modified mouse models. The researchers reported that Car3 was highly activated in osteoblast-lineage cells during early embryonic cranial development, especially between embryonic days 14.5 and 15.5—a period associated with active bone mineralization. Car3 expression was also observed in limb, rib, and spinal bones. In young mice, Car3 expression correlated with collagen-producing osteoblasts but shifted toward adipocytes in aged mice.
Dr. Song said, "As osteoblasts have critical roles in skeletal development, we examined the molecular mechanisms involved in osteoblast differentiation, which can potentially aid in developing novel therapeutic strategies for bone disorders." The team found that RUNX2 directly regulated Car3 expression during osteoblast differentiation. Further analysis revealed that CAR3 formed a molecular complex with collagen type I alpha 1 (COL1A1) and recruited bone sialoprotein (BSP), promoting collagen intrafibrillar mineralization—an essential process for generating strong bone tissue.
Functional experiments showed that deleting Car3 in Prx1-lineage skeletal stem cells did not affect early femur development but led to impaired osteoblast activity, defective collagen mineralization, reduced bone formation, and decreased bone density in adult mice.
To explore therapeutic applications, the researchers implanted recombinant CAR3-functionalized collagen scaffolds into mouse models with bone defects. After eight weeks, these scaffolds significantly enhanced new bone formation by increasing volume and promoting matrix mineralization.
Prof. Zhang said, "Our mouse experiments revealed that application of collagen functionalized with CAR3 promoted bone formation. Thus, the regulatory effects of Car3 on osteoblast differentiation can be harnessed to treat bone disorders." The study highlights the potential of CAR3-based biomaterials for treating osteoporosis and other conditions involving impaired bone regeneration.
