Intra-Bone Marrow Administration of miR-140-3p Improves Bone Metabolism in a Growing Senescence-Accelerated Mouse Prone 6 Strain

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The authors reported that treating the senescence-accelerated mice with a Lipo NanoParticle (LNP) containing miR-140-3p, can improve bone metabolism including greater bone volume, trabecular thickness, and osteoid thickness. There are some changes in the results, but I think there are some limitations in this study.

1. There are only 3 mice in one group, which is indeed a small sample size. This small number can limit the statistical power of the study and may not adequately account for natural biological variation among individual mice. Increasing the number of mice per group to at least six, would likely provide more reliable and reproducible data.
2. The imaging results shown in Figure 2-6 all lack quantifications. Quantitative analysis would give more concrete data to support the visual findings and conclusions drawn from the images. Including statistical comparisons and quantified measurements (e.g., bone density, trabecular number) would strengthen the study's findings.
3. Are there any other bone formation markers besides from Gla also changes in the treated mice? A broader panel of bone formation markers, such as alkaline phosphatase (ALP), osteocalcin (OCN, in its undercarboxylated form), or collagen type I, could provide a more comprehensive view of the changes in bone metabolism. This would help to confirm the biological significance of the miR-140-3p treatment more robustly.
4. The reasons of using Senescence-accelerated mouse (SAM) strains in experiments.

Author Response

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Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

Comments and Suggestions for Authors are attached as a file. 

Comments for author File: Comments.pdf

Author Response

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Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

Here are some points need to be further checked.

1. Ensure that the number of samples ('n') is clearly indicated in both Table 1 and Table 2. Besides, for individual results, consider adding a supplementary section or appendix where detailed data for each subject or sample is presented. This can include individual measurements or values that contributed to the group statistics summarized in the tables.
2. Why does the any other bone formation marker ALP, was not different among groups? Consider mentioning these points in the discussion section.
3. Ensure that the definition of Glu, the undercarboxylated form of osteocalcin (OCN), is introduced earlier in the introduction. It is better to introduce it in the first paragraph where OCN is first mentioned, along with its relevance to the study.
4. The format of text around the tables are in a mess, please check line 208-211, line 231-241

Comments on the Quality of English Language

No, thank you!

Author Response

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Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

All requirements are adequately revised for acceptance. 

Author Response

We appreciate your warm comments.