Tmem100- and Acta2-Lineage Cells Contribute to Implant Osseointegration in a Mouse Model

Abstract

Metal implants are commonly used in orthopedic surgery. The mechanical stability and longevity of implants depend on adequate bone deposition along the implant surface. The cellular and molecular mechanisms underlying peri‐implant bone formation (ie, osseointegration) are incompletely understood. Herein, our goal was to determine the specific bone marrow stromal cell populations that contribute to bone formation around metal implants. To do this, we utilized a mouse tibial implant model that is clinically representative of human joint replacement procedures. Using a lineage‐tracing approach, we found that both Acta2.creERT2 and Tmem100.creERT2 lineage cells are involved in peri‐implant bone formation, and Pdgfra‐ and Ly6a/Sca1‐expressing stromal cells (PαS cells) are highly enriched in both lineages. Single‐cell RNA‐seq analysis indicated that PαS cells are quiescent in uninjured bone tissue; however, they express markers of proliferation and osteogenic differentiation shortly after implantation surgery. Our findings indicate that PαS cells are mobilized to repair bone tissue and participate in implant osseointegration after surgery. Biologic therapies targeting PαS cells might improve osseointegration in patients undergoing orthopedic procedures. © 2021 American Society for Bone and Mineral Research (ASBMR).

Activin A marks a novel progenitor cell population during fracture healing and reveals a therapeutic strategy

“…Interestingly, Lrrc15 is also a marker for PPCs in our study. In addition, abundant αSMA+ stromal cells were recently reported to occur around the injury site after metal implant surgery in mouse tibiae ( Vesprey et al, 2021 ). In sum, acute injury resulting from bone fracture, metal implantation, or other insults appears to elicit a common and forceful repair response that is coupled to the emergence of progenitors with a myofibroblast-like phenotype.…”

The Role of a Lung Vascular Endothelium Enriched Gene TMEM100

“…Our recent studies using immunostaining against TMEM100 in different human organs showed that TMEM100 is highly expressed in the human lung ECs but not in any other organ (heart, liver, kidney) ECs [ 14 ], suggesting that TMEM100 might play an important role in lung vasculature hemostasis. Moreover, several groups have generated Tmem100 reporter mouse lines [ 9 , 10 , 14 , 15 , 16 ] ( Table 1 ). Moon et al and Somekawa et al showed that Tmem100 reporter expression was detected in the major arteries in E10.5 and E11.5 embryos [ 9 , 10 ].…”

“…Moon et al showed that Tmem100 expression was also found in the mammary glands, notochord, and ventral regions of the neural tube [ 9 ]. Vesprey et al employed a Tmem100-creERT2; Ai14 reporter mouse line and found that postnatal Tmem100-creERT2 expression marked endothelial cells, PaS cells, osteoblasts, and proliferating zone chondrocytes [ 16 ]. Through colocalization with a pan-neuronal marker, PGP9.5, Eisenman et al found the localization of TMEM100 immunoreactivity in the mice and human enteric nervous system and the mice’s central and peripheral nervous system in addition to arterial ECs [ 12 ].…”