Peter J Delisser

Wnt16 Is Associated with Age-Related Bone Loss and Estrogen Withdrawal in Murine Bone

Genome Wide Association Studies suggest that Wnt16 is an important contributor to the mechanisms controlling bone mineral density, cortical thickness, bone strength and ultimately fracture risk. Wnt16 acts on osteoblasts and osteoclasts and, in cortical bone, is predominantly derived from osteoblasts. This led us to hypothesize that low bone mass would be associated with low levels of Wnt16 expression and that Wnt16 expression would be increased by anabolic factors, including mechanical loading. We therefore investigated Wnt16 expression in the context of ageing, mechanical loading and unloading, estrogen deficiency and replacement, and estrogen receptor α (ERα) depletion. Quantitative real time PCR showed that Wnt16 mRNA expression was lower in cortical bone and marrow of aged compared to young female mice. Neither increased nor decreased (by disuse) mechanical loading altered Wnt16 expression in young female mice, although Wnt16 expression was decreased following ovariectomy. Both 17β-estradiol and the Selective Estrogen Receptor Modulator Tamoxifen increased Wnt16 expression relative to ovariectomy. Wnt16 and ERβ expression were increased in female ERα-/- mice when compared to Wild Type. We also addressed potential effects of gender on Wnt16 expression and while the expression was lower in the cortical bone of aged males as in females, it was higher in male bone marrow of aged mice compared to young. In the kidney, which we used as a non-bone reference tissue, Wnt16 expression was unaffected by age in either males or females. In summary, age, and its associated bone loss, is associated with low levels of Wnt16 expression whereas bone loss associated with disuse has no effect on Wnt16 expression. In the artificially loaded mouse tibia we observed no loading-related up-regulation of Wnt16 expression but provide evidence that its expression is influenced by estrogen receptor signaling. These findings suggest that while Wnt16 is not an obligatory contributor to regulation of bone mass per se, it potentially plays a role in influencing pathways associated with regulation of bone mass during ageing and estrogen withdrawal.

Static hydraulic urethral sphincter for treatment of urethral sphincter mechanism incompetence in 11 dogs

OBJECTIVE To review the postoperative results and complications associated with urethral sphincter mechanism incompetence managed with a static hydraulic urethral sphincter. METHODS Case records and a telephone owner questionnaire were retrospectively used to assess postoperative urinary continence scores (1 - dripping constantly to 10 - completely dry) and presence and frequency of complications. RESULTS Eleven spayed females were included. Median continence score/10 (range) awarded preoperatively was 3 (2 to 6), and scores at two weeks, three and six months were 8 (4 to 10), 9 (4 to 10) and 8 (4 to 10), respectively. At the last survey, the median continence score of 9 (5 to 10) was significantly better (P=0·004) than before surgery. Complete continence was achieved in 36·4% of dogs. The median (range) follow-up time was 412 (118 to 749) days. Complications occurred in 9 of 11 dogs and included dysuria (n=7), bacterial cystitis (n=7), longer urination time (n=8), urinary retention (n=3), haematuria (n=1), pain (n=3) and incisional seroma (n=3). CLINICAL SIGNIFICANCE Static hydraulic urethral sphincter was frequently associated with minor complications but no major complications (i.e. those requiring further surgery). Continence scores were significantly improved compared with those before surgery, with the possibility of further improvement following inflation of the sphincter.

Planar Cell Polarity Aligns Osteoblast Division in Response to Substrate Strain

Exposure of bone to dynamic strain increases the rate of division of osteoblasts and also influences the directional organization of the cellular and molecular structure of the bone tissue that they produce. Here, we report that brief exposure to dynamic substrate strain (sufficient to rapidly stimulate cell division) influences the orientation of osteoblastic cell division. The initial proliferative response to strain involves canonical Wnt signaling and can be blocked by sclerostin. However, the strain‐related orientation of cell division is independently influenced through the noncanonical Wnt/planar cell polarity (PCP) pathway. Blockade of Rho‐associated coiled kinase (ROCK), a component of the PCP pathway, prevents strain‐related orientation of division in osteoblast‐like Saos‐2 cells. Heterozygous loop‐tail mutation of the core PCP component van Gogh‐like 2 (Vangl2) in mouse osteoblasts impairs the orientation of division in response to strain. Examination of bones from Vangl2 loop‐tail heterozygous mice by µCT and scanning electron microscopy reveals altered bone architecture and disorganized bone‐forming surfaces. Hence, in addition to the well‐accepted role of PCP involvement in response to developmental cues during skeletal morphogenesis, our data reveal that this pathway also acts postnatally, in parallel with canonical Wnt signaling, to transduce biomechanical cues into skeletal adaptive responses. The simultaneous and independent actions of these two pathways appear to influence both the rate and orientation of osteoblast division, thus fine‐tuning bone architecture to meet the structural demands of functional loading.

Temporally separated bilateral anal sac gland carcinomas in four dogs

Anal sac gland carcinoma arising from the apocrine secretory epithelium in the anal sac wall, is locally invasive and highly metastatic. The majority of anal sac gland carcinomas are unilateral on presentation, but bilateral tumours have been identified. This case series presents the outcome of four unique cases of unilateral anal sac gland carcinoma which subsequently developed contralateral anal sac gland carcinoma 50 to 390 days after removal of the initial tumour. Median survival was 1035 days after initial diagnosis and 807 days after diagnosis of the second anal sac gland carcinoma.

Old age and the associated impairment of bones' adaptation to loading are associated with transcriptomic changes in cellular metabolism, cell-matrix interactions and the cell cycle.

In old animals, bones ability to adapt its mass and architecture to functional load-bearing requirements is diminished, resulting in bone loss characteristic of osteoporosis. Here we investigate transcriptomic changes associated with this impaired adaptive response. Young adult (19-week-old) and aged (19-month-old) female mice were subjected to unilateral axial tibial loading and their cortical shells harvested for microarray analysis between 1 h and 24 h following loading (36 mice per age group, 6 mice per loading group at 6 time points). In non-loaded aged bones, down-regulated genes are enriched for MAPK, Wnt and cell cycle components, including E2F1. E2F1 is the transcription factor most closely associated with genes down-regulated by ageing and is down-regulated at the protein level in osteocytes. Genes up-regulated in aged bone are enriched for carbohydrate metabolism, TNFα and TGFβ superfamily components. Loading stimulates rapid and sustained transcriptional responses in both age groups. However, genes related to proliferation are predominantly up-regulated in the young and down-regulated in the aged following loading, whereas those implicated in bioenergetics are down-regulated in the young and up-regulated in the aged. Networks of inter-related transcription factors regulated by E2F1 are loading-responsive in both age groups. Loading regulates genes involved in similar signalling cascades in both age groups, but these responses are more sustained in the young than aged. From this we conclude that cells in aged bone retain the capability to sense and transduce loading-related stimuli, but their ability to translate acute responses into functionally relevant outcomes is diminished.

Osteomyelitis and fracture callus abscessation secondary to a foreign body reaction in a traumatic open fracture of the zygomatic bone of a puppy

A five-month-old male labrador retriever presented with a large (6×3×5 cm) firm swelling associated with the right zygomatic arch. The dog suffered a bite wound two months previously, causing puncture wounds dorsal to the orbit where radiographs demonstrated a minimally displaced fracture of the zygomatic arch and surrounding soft, fluctuant swelling. Following three to four weeks of conservative management, the swelling had partially ossified. CT of the skull demonstrated a large cavitary osseous lesion of the right zygomatic arch associated with the previous fracture site. A lateral approach was used to perform marginal excision of the mass, preserving the eye. Histopathology of the mass revealed woven bone formation, granulation tissue lining the cavity and a fragment of plant material within the cavity. The recovery from surgery was unremarkable, and the dog did not suffer any intraoperative or postoperative complications. The dog was clinically normal at follow-up 21 months post surgery.

A survey of surgical draping practices in small-animal practice in the UK

Veterinary practices in the United Kingdom were surveyed to compare their surgical draping practices with Royal College of Veterinary Surgeons (RCVS) accreditation tier and other surgery-related factors. Using descriptive statistics and logistic or ordinal regression analysis (where appropriate), the relationships between draping material and accreditation tier and other surgery-related factors were assessed. Procedures were categorised as short or long. Two hundred and sixty-nine surveys were completed. Reusable drapes were used in 66 per cent of practices. Antibiotics were administered routinely in 38 per cent of short and 93 per cent of long procedures. Practices accredited as a Veterinary Hospital (VH) were 6.3–7.2 (short and long surgeries, respectively) times more likely to use disposable drapes, when compared with non-accredited practices. Use of dedicated surgical attire, draping the whole animal/table, and routine antibiotic usage were also positively correlated with disposable drape usage. Fifty-one per cent of practices rated infection rate as most important when choosing drape material. ‘Best practice’ techniques are associated with lower importance given to infection rate, and higher importance given to financial cost, when choosing drape material. Disposable drape use correlates with RCVS accreditation and with other aspects of surgical technique. Importance ratings awarded correlate with best practice procedures. Clinical relevance ‘Best practice’ draping procedures, that are not governed by RCVS accreditation scheme, are also more frequently performed in accredited VHs.