TY - JOUR
T1 - Dmp1 Lineage Cells Contribute Significantly to Periosteal Lamellar Bone Formation Induced by Mechanical Loading But Are Depleted from the Bone Surface During Rapid Bone Formation
AU - Harris, Taylor L.
AU - Silva, Matthew J.
N1 - Publisher Copyright:
© 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
PY - 2022/3
Y1 - 2022/3
N2 - Previous work has shown that osteoprogenitor cells (Prx1+) and pre-osteoblasts (Osx+) contribute to mechanical loading-induced bone formation. However, the role of mature Dmp1-expressing osteoblasts has not been reported. In this study we assessed the contribution of osteoblast lineage cells to bone formation at an early time point following mechanical loading (day 8 from onset of loading). We labeled Osx-expressing and Dmp1-expressing cells in inducible Osx and Dmp1 reporter mice (iOsx-Ai9, iDmp1-Ai9), respectively, 3 weeks before loading. Mice were then loaded daily for 5 days (days 1–5) and were dosed with 5-ethynyl-2′-deoxyuridine (EdU) in their drinking water until euthanasia on day 8. Mice were loaded to lamellar and woven bone inducing stimulation (−7 N/1400 με, −10 N/2000 με) to assess differences in these processes. We found varied responses in males and females to the loading stimuli, inducing modest lamellar (females, −7 N), moderate lamellar (males, −10 N), and robust woven (females, −10 N) bone. Overall, we found that preexisting (ie, lineage positive) Osx-expressing and Dmp1-expressing cells contribute largely to the bone formation response, especially during modest bone formation, while our results stuggest that other (non-lineage–positive) cells support the sustained bone formation response during rapid bone formation. With moderate or robust levels of bone formation, a decrease in preexisting Osx-expressing and Dmp1-expressing cells at the bone surface occurred, with a near depletion of Dmp1-expressing cells from the surface in female mice loaded to −10 N (from 52% to 11%). These cells appeared to be replaced by lineage-negative cells from the periosteum. We also found a dose response in proliferation, with 17% to 18% of bone surface cells arising via proliferation in modest lamellar, 38% to 53% in moderate lamellar, and 59% to 81% in robust woven bone formation. In summary, our results show predominant contributions by preexisting Osx and Dmp1 lineage cells to loading-induced lamellar bone formation, whereas recruitment of earlier osteoprogenitors and increased cell proliferation support robust woven bone formation.
AB - Previous work has shown that osteoprogenitor cells (Prx1+) and pre-osteoblasts (Osx+) contribute to mechanical loading-induced bone formation. However, the role of mature Dmp1-expressing osteoblasts has not been reported. In this study we assessed the contribution of osteoblast lineage cells to bone formation at an early time point following mechanical loading (day 8 from onset of loading). We labeled Osx-expressing and Dmp1-expressing cells in inducible Osx and Dmp1 reporter mice (iOsx-Ai9, iDmp1-Ai9), respectively, 3 weeks before loading. Mice were then loaded daily for 5 days (days 1–5) and were dosed with 5-ethynyl-2′-deoxyuridine (EdU) in their drinking water until euthanasia on day 8. Mice were loaded to lamellar and woven bone inducing stimulation (−7 N/1400 με, −10 N/2000 με) to assess differences in these processes. We found varied responses in males and females to the loading stimuli, inducing modest lamellar (females, −7 N), moderate lamellar (males, −10 N), and robust woven (females, −10 N) bone. Overall, we found that preexisting (ie, lineage positive) Osx-expressing and Dmp1-expressing cells contribute largely to the bone formation response, especially during modest bone formation, while our results stuggest that other (non-lineage–positive) cells support the sustained bone formation response during rapid bone formation. With moderate or robust levels of bone formation, a decrease in preexisting Osx-expressing and Dmp1-expressing cells at the bone surface occurred, with a near depletion of Dmp1-expressing cells from the surface in female mice loaded to −10 N (from 52% to 11%). These cells appeared to be replaced by lineage-negative cells from the periosteum. We also found a dose response in proliferation, with 17% to 18% of bone surface cells arising via proliferation in modest lamellar, 38% to 53% in moderate lamellar, and 59% to 81% in robust woven bone formation. In summary, our results show predominant contributions by preexisting Osx and Dmp1 lineage cells to loading-induced lamellar bone formation, whereas recruitment of earlier osteoprogenitors and increased cell proliferation support robust woven bone formation.
KW - ANIMAL MODELS
KW - BONE MATRIX
KW - CELLS OF BONE
KW - GENETIC ANIMAL MODELS
KW - MATRIX MINERALIZATION
KW - OSTEOBLASTS
UR - http://www.scopus.com/inward/record.url?scp=85122260873&partnerID=8YFLogxK
U2 - 10.1002/jbm4.10593
DO - 10.1002/jbm4.10593
M3 - Article
C2 - 35309865
AN - SCOPUS:85122260873
SN - 2473-4039
VL - 6
JO - JBMR Plus
JF - JBMR Plus
IS - 3
M1 - e10593
ER -