Lnk Deficiency Leads to TPO-Mediated Osteoclastogenesis and Increased Bone Mass Phenotype.

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. © 2017 Wiley Periodicals, Inc.

Paternal Preferences, Perspectives, and Involvement in Perinatal Decision Making.

IMPORTANCE: Despite increasing attention to the importance of father involvement during pregnancy, the literature on fathers' roles in perinatal decision making is scant. OBJECTIVE: The aim of this study was to conduct a narrative review of the literature exploring fathers' preferences, perspectives, and involvement in perinatal decision making. EVIDENCE ACQUISITION: We searched PubMed, Ovid, EMBASE, Cochrane Library, and CINAHL databases using the terms father, spouse(s), husband, and paternal separately with the combined terms of attitude, preference, involvement, influence, informed consent, decision making, pregnancy, labor induction, genetic testing, prenatal diagnosis, amniocentesis, fetal surgery, genetic abnormalities, congenital anomalies, birth defects, perinatal, and antenatal. The search was limited to English-language studies that were published anytime and conducted between July and September 2018. RESULTS: The initial search identified 616 articles; 13 articles met criteria for inclusion. Fathers view themselves as serving distinct roles in perinatal decision making and have specific informational needs that would support their involvement in decision making. Although fathers want to support their partners and learn about fetal health, they often feel excluded from perinatal screening decisions. Mothers and fathers also have different needs, concerns, and preferences regarding key perinatal decisions that, if unresolved, can impact the couples' relationship and perinatal outcomes. CONCLUSIONS: Findings provide import insights into the distinct experiences, roles, needs, and perspectives of fathers facing perinatal decision making. RELEVANCE: Advancing research and policy on fathers' involvement in perinatal decision making could lead to a paradigm shift in how maternity care is structured, how obstetric services are delivered, and how perinatal interventions are designed and implemented.