Fig. 1: The ablation of the endoplasmic tail of the DCSTAMP protein elicits an augmentation in bone mass in mice. | Experimental & Molecular Medicine

Fig. 1: The ablation of the endoplasmic tail of the DCSTAMP protein elicits an augmentation in bone mass in mice.

From: A novel DCSTAMP antagonist impedes preosteoclast fusion via modulation of RAP1B–RAC1-mediated cytoskeletal remodeling

Fig. 1: The ablation of the endoplasmic tail of the DCSTAMP protein elicits an augmentation in bone mass in mice.The alternative text for this image may have been generated using AI.

a The regional association diagram pertaining to the DCSTAMP locus is delineated. The x axis denotes the genomic coordinates at chr11: 105342024-105378917 (hg19). Each data point signifies a distinct genetic variant situated within this specific genomic interval. Top: a data point panel exhibiting the correlation of genetic variants with eBMD, with the most statistically significant single-nucleotide polymorphism, rs2514663 (P = 4.60 × 10−4), highlighted in a regal purple hue. Bottom: a data point panel illustrates the relationship of genetic variants with DCSTAMP expression. The most notable DCSTAMP eQTL within osteoclast-like cellular cultures, rs2458418 (P = 5.36 × 10−11), is also accentuated in a striking purple shade. b The sixth transmembrane (T6) segments of the DCSTAMP protein are denoted by a distinct yellow coloration at the base; the single amino acid substitution (L to F) identified in Paget’s disease is indicated by a crimson arrow; the ITIM is signified by a scarlet bracket. c The SpRY–Cas9 endonuclease (highlighted in yellow) is precisely directed toward the DCSTAMP DNA via an sgRNA encompassing a 20-nucleotide guiding sequence (depicted in blue), leading to a frameshift mutation (displayed in a verdant lower hue). d The diagram elucidates that the frameshift mutation results in the inactivation of the cytoplasmic tail of the DCSTAMP protein. e The Sanger sequencing of WT and Dcstamp-tail−/− mice. f The representative MicroCT analysis of the distal femur is presented for WT mice subjected to sham surgery (WT Sham), DCSTAMP endoplasmic tail knockout mice undergoing Sham surgery (Dcstamp-tail−/− Sham), WT mice undergoing OVX surgery (WT OVX) and DCSTAMP endoplasmic tail knockout mice undergoing OVX surgery (Dcstamp-tail−/− OVX). g–j Computations derived from MicroCT scans encompassing BV/TV (g), bone mineral density (BMD) (h), trabecular number (Tb.N), trabecular thickness (Tb.Th), trabecular separation (Tb.Sp) (i) and cortical thickness (Ct.Th) (j). k The enumeration of the Tb.Ar derived from H&E staining. l An illustrative representation of H&E staining results from distal femoral sections. Scale bar, 200 μm. m The circulating levels of osteoclastic markers, inclusive of CTX-1 and TRACP5b. n The circulating levels of osteoblastic markers, encompassing PINP and OCN. N = 6 per experimental group. The data are presented as mean ± s.d. with individual data points depicted as dots. Statistical significance levels are denoted as follows: *P < 0.05, **P < 0.01, ***P < 0.001; ns, not significant.

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