Background: Recent studies have suggested osteocytes as key players in mechanosensation and skeletal metabolism. Results: Simulated microgravity induces an autonomous up-regulation of SOST/sclerostin and RANKL/OPG in a novel osteocytic cell line, Ocy454. Conclusion: Mechanical loading regulates intrinsic osteocyte responses in concert with hormonal and cytokine inputs. Significance: Learning how osteocytes sense mechanical loads would enable novel interventions to prevent disuse-induced bone loss.

Intermittent administration of parathyroid hormone (PTH) increases bone mass, at least in part, by increasing osteoblast number. One possible source of osteoblasts might be conversion of inactive lining cells to osteoblasts, and indirect evidence is consistent with this hypothesis. To better understand the possible effect of PTH on lining cell activation, a lineage tracing study was conducted using an inducible gene system. Dmp1-CreERt2 mice were crossed with ROSA26R reporter mice to render targeted mature osteoblasts and their descendents, lining cells and osteocytes, detectable by X-gal staining. Dmp1-CreERt2(+):ROSA26R mice were injected with 0.25 mg 4-OH-tamoxifen (4-OHTam) on postnatal day 3, 5, 7, 14, and 21. The animals were sacrificed on postnatal day 23, 33 or 43 (2, 12 or 22 days after the last 4-OHTam injection). On day 43, mice were challenged with a subcutaneous injection of human PTH (1–34, 80 μg/kg) or vehicle once daily for 3 days. By 22 days after the last 4-OHTam injection, most X-gal (+) cells on the periosteal surfaces of both the calvaria and tibia were flat. Moreover, bone formation rate and collagen I(α1) mRNA expression were decreased at day 43 compared to day 23. After 3 days of PTH injections, the thickness of X-gal (+) cells increased, as did their expression of osteocalcin and collagen I(α1) mRNA. Electron microscopy revealed X-gal-associated chromagen particles in both thin cells prior to PTH administration and cuboidal cells following PTH administration. These data support the hypothesis that intermittent PTH treatment can increase osteoblast number by converting lining cells to mature osteoblasts in vivo.

Key Points• Deletion of Gs␣ in osteocytes induces severe osteopenia and a dramatic expansion of cells of the myeloid lineage.• Osteocytes regulate hematopoiesis and specifically contribute to myelopoiesis by secreting proliferative factors such as G-CSF.

Parathyroid hormone (PTH) is a major physiologic regulator of calcium, phosphorous and skeletal homeostasis. Cells of the osteoblastic lineage are key targets of PTH action in bone, and recent evidence suggests that osteocytes might be important in the anabolic effects of PTH. To understand the role of PTH signaling through the PTH/PTHrP receptors (PPR) in osteocytes and to determine the role(s) of these cells in mediating the effects of the hormone, we have generated mice in which PPR expression is specifically ablated in osteocytes. Transgenic mice in which the 10Kb-Dmp1 promoter drives a tamoxifen-inducible Cre –recombinase were mated with animals in which exon1 of PPR is flanked by Lox-P sites. In these animals, osteocyte-selective PPR knockout (Ocy-PPRcKO mice) could be induced by administration of tamoxifen. Histological analysis revealed a reduction in trabecular bone and mild osteopenia in Ocy-PPRcKO mice. Reduction of trabeculae number and thickness was also detected by μCT analysis whereas BV/TV% was unchanged. These findings were associated with an increase in Sost and sclerostin expression. When Ocy-PPRcKO mice were subjected to a low calcium diet, to induce secondary hyperparathyroidism, their blood calcium levels were significantly lower than littermate controls. Moreover, PTH was unable to suppress Sost and sclerostin expression in the Ocy-PPRcKO animals, suggesting an important role of PTH signaling in osteocytes for proper bone remodeling and calcium homeostasis.

Background: Osteocytes, the most abundant cells in adult bone, express PPR. Results: Mice with constitutive PPR deletion in osteocytes demonstrate blunted anabolic and catabolic bone responses and the inability to recruit osteoblasts and osteoclasts upon PTH administration. Conclusion: PPR in osteocytes is needed for a full skeletal response to PTH administration. Significance: PPR signaling in osteocytes is necessary for PTH-driven anabolic effects during osteoporosis therapy.

Background— Medical journals use social media to distribute the findings of published articles. Whether social media exposure to original articles improves article impact metrics is uncertain. Methods and Results— Articles were randomized to receive targeted social media exposure from Circulation , including postings on the journal’s Facebook and Twitter feeds. The primary end point was 30-day article page views. We conducted an intention-to-treat analysis comparing article page views by the Wilcoxon Rank sum test between articles randomized to social media as compared with those in the control group, which received no social media from Circulation . Prespecified subgroups included article type (population/clinical/basic), US versus non-US corresponding author, and whether the article received an editorial. Overall, 243 articles were randomized: 121 in the social media arm and 122 in the control arm. There was no difference in median 30-day page views (409 [social media] versus 392 [control], P =0.80). No differences were observed by article type (clinical, population, or basic science; P =0.19), whether an article had an editorial ( P =0.87), or whether the corresponding author was from the United States ( P =0.73). Conclusions— A social media strategy for a cardiovascular journal did not increase the number of times an article was viewed. Further research is necessary to understand and quantify the ways in which social media can increase the impact of published cardiovascular research.

BackgroundA prior randomized controlled trial of social media exposure at Circulation determined that social media did not increase 30‐day page views. Whether insufficient social media intensity contributed to these results is uncertain.Methods and ResultsOriginal article manuscripts were randomized to social media exposure compared with no social media exposure (control) at Circulation beginning in January 2015. Social media exposure consisted of Facebook and Twitter posts on the journal's accounts. To increase social media intensity, a larger base of followers was built using advertising and organic growth, and posts were presented in triplicate and boosted on Facebook and retweeted on Twitter. The primary outcome was 30‐day page views. Stopping rules were established at the point that 50% of the manuscripts were randomized and had 30‐day follow‐up to compare groups on 30‐day page views. The trial was stopped for futility on September 26, 2015. Overall, 74 manuscripts were randomized to receive social media exposure, and 78 manuscripts were randomized to the control arm. The intervention and control arms were similar based on article type (P=0.85), geographic location of the corresponding author (P=0.33), and whether the manuscript had an editorial (P=0.80). Median number of 30‐day page views was 499.5 in the social media arm and 450.5 in the control arm; there was no evidence of a treatment effect (P=0.38). There were no statistically significant interactions of treatment by manuscript type (P=0.86), by corresponding author (P=0.35), by trimester of publication date (P=0.34), or by editorial status (P=0.79).ConclusionsA more intensive social media strategy did not result in increased 30‐day page views of original research.

SUMMARY A method for induction of subarachnoid hemorrhage (SAH) in a rat model is described. Resolution of the hemorrhage was documented photographically and microscopically at intervals from 1 hr to 8 days. Photographs indicated that most of the hemorrhage was resorbed within 3 days, an observation confirmed microscopically by the amount of red blood cells in the subarachnoid space. Significant cerebral vasospasm was documented within the first 2 days after the induction of hemorrhage with the basilar artery returning to baseline values at an average of 3 days followed by moderate dilatation at 5 to 8 days. 10 -u The possibility of using a smaller, less expensive laboratory animal has not been thoroughly investigated. The present investigation sought to determine whether the rat was a suitable animal for the study of SAH with regard to the mode of SAH induction, its time course of resolution and the degree of cerebral vasospasm produced. Materials and MethodsAll animals were 400-600 g male Sprague-Dawley rats. They were anesthetized with intraperitoneal injections of sodium nembutal (40-50 mg/kg). The rats were placed in the supine position, the ventral portion of the neck shaved, and a midline incision approximately 2.5 cm in length made. The trachea was exposed and an endotracheal tube (ID 0.062", OD 0.082") inserted orally, and visualized entering the exposed trachea. Repeated suction ensured maintenance of an adequate airway. Using an operating microscope, the cervical musculature and carotid arteries were retracted to expose a 15-20 mm 2 area of clivus. A midline craniectomy (less than 2 mm 2 ) was performed using a #23A Horico diamond burr to expose the normally transparent dura and underlying basilar artery. A tungsten microelectrode, drawn to a 40-60 micron tip, was positioned over the exposed basilar artery using a stereotactic device ( fig. 1). The tip was advanced through the intact dural and arachnoid membranes and into the lumen of the basilar artery. SAH was induced upon slow withdrawal of the tungsten tip. The subarachnoid progression of the hemorrhage was visualized microscopically through the craniectomy. Gelfoam® (absorbable gelatin sponge, The Upjohn Company, Kalamazoo, MI) was placed at the craniectomy site and the neck incision closed with skin clips. The endotracheal tube was left in place approximately 1-2 hr postoperatively until the animal had recovered from the effects of the anesthesia and was without obvious respiratory distress.The site of the SAH was reexposed 1 hr (acute), or 1, 2, 3, 5, and 8 days postoperatively. Animals used acutely were maintained on sodium nembutal postoperatively. After recovering from initial surgery, all chronic animals were reanesthetized, tracheotomized, and intubated. The clivus was reexposed and the craniectomy enlarged with the diamond burr revealing a larger segment of the basilar artery (approximately 7-10 mm). The dura was then carefully removed allowing better visualization of the underlying basilar artery and brainstem. Photographs were taken thr...