Key result
Lnk-deficient mice demonstrated a 2.5-fold greater bone volume fraction compared to wild-type mice, suggesting impaired osteoclast function in vivo despite increased osteoclast numbers.
Why the study?
Does Lnk deficiency alter bone mass and osteoclastogenesis in mice?
Does Lnk deficiency alter bone mass and osteoclastogenesis in mice?
Lnk deficiency leads to a high bone mass phenotype in mice, likely driven by impaired osteoclast function in vivo and altered osteoblast activity.
Answers are grounded in this paper and cite their sources.
Lnk deficiency increases murine bone mass via osteoclast impairment; leaves open any human therapeutic relevance.
The Lnk adapter protein negatively regulates the signaling of thrombopoietin (TPO), the main megakaryocyte (MK) growth factor. Lnk-deficient (−/−) mice have increased TPO signaling and increased MK number. Interestingly, several mouse models exist in which increased MK number leads to a high bone mass phenotype. Here we report the bone phenotype of these mice. MicroCT and static histomorphometric analyses at 20 weeks showed the distal femur of Lnk−/− mice to have significantly higher bone volume fraction and trabecular number compared to wild-type (WT) mice. Notably, despite a significant increase in the number of osteoclasts (OC), and decreased bone formation rate in Lnk−/− mice compared to WT mice, Lnk−/− mice demonstrated a 2.5-fold greater BV/TV suggesting impaired OC function in vivo. Additionally, Lnk−/− mouse femurs exhibited non-significant increases in mid-shaft cross-sectional area, yet increased periosteal BFR compared to WT femurs was observed. Lnk−/− femurs also had non-significant increases in polar moment of inertia and decreased cortical bone area and thickness, resulting in reduced bone stiffness, modulus, and strength compared to WT femurs. Of note, Lnk is expressed by OC lineage cells and when Lnk−/− OC progenitors are cultured in the presence of TPO, significantly more OC are observed than in WT cultures. Lnk is also expressed in osteoblast (OB) cells and in vitro reduced alkaline phosphatase activity was observed in Lnk−/− cultures. These data suggest that both direct effects on OB and OC as well as indirect effects of MK in regulating OB contributes to the observed high bone mass. J. Cell. Biochem. 118: 2231–2240, 2017.
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Olivos et al. (2017) studied Lnk deficiency bone mass phenotype. Lnk deficiency vs. Wild-type (WT) mice was evaluated on Bone volume fraction (BV/TV) and trabecular number (2.5-fold greater BV/TV). Lnk-deficient mice demonstrated a 2.5-fold greater bone volume fraction compared to wild-type mice, suggesting impaired osteoclast function in vivo despite increased osteoclast numbers.
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