MMP14 is a novel target of PTH signaling in osteocytes that controls resorption by regulating soluble RANKL production.

Parathyroid hormone (PTH) affects the skeleton by acting on osteocytes (Ots) in bone through yet unclear mechanisms. We report that matrix metalloproteinase 14 (MMP14) expression/activity are increased in bones from mice with genetic constitutive activation (ca) of the PTH receptor 1 (PTH1R) in Ots (caPTH1ROt) and in bones from mice exposed to elevated PTH levels but not in mice lacking [conditional knockout (cKO)] the PTH1R in Ots (cKOPTH1ROt). Furthermore, PTH upregulates MMP14 in human bone cultures and in Ot-enriched bones from floxed control mice but not from cKOPTH1ROt mice. MMP14 activity increases soluble receptor activator of NF-κΒ ligand production, which in turn, stimulates osteoclast differentiation and resorption. Pharmacologic inhibition of MMP14 activity reduced the high bone remodeling exhibited by caPTH1ROt mice or induced by chronic PTH elevation and decreased bone resorption but allowed full stimulation of bone formation induced by PTH injections, thereby potentiating bone gain. Thus, MMP14 is a new member of the intricate gene network activated in Ots by PTH1R signaling that can be targeted to adjust the skeletal responses to PTH in favor of bone preservation.-Delgado-Calle, J., Hancock, B., Likine, E. F., Sato, A. Y., McAndrews, K., Sanudo, C., Bruzzaniti, A., Riancho, J. A., Tonra, J. R., Bellido, T. MMP14 is a novel target of PTH signaling in osteocytes that controls resorption by regulating soluble RANKL production.

Safety and Efficacy of Synthetic Mesh for Ventral Hernia Repair in a Contaminated Field.

BACKGROUND: Controversy remains about appropriate mesh selection during ventral hernia repair (VHR) in a contaminated field. Fear of mesh infection has led to increased use of biologic and absorbable synthetic meshes rather than permanent synthetic mesh in these cases. We report the safety and efficacy of permanent synthetic mesh during contaminated VHR. STUDY DESIGN: Retrospective review of our database identified all cases of contaminated VHR from July 2007 to May 2019. Student's t-test and Wilcoxon rank sum were used to analyze continuous variables, and discrete variables with Fisher's or Kruskal-Wallis test. RESULTS: There were 541 contaminated cases: 245 clean-contaminated, 214 contaminated, and 82 dirty cases. Suture repair was performed in 46 patients, biologic mesh was used in 38, absorbable synthetic mesh in 55, and permanent synthetic mesh in 402. Mesh was extraperitoneal in 97% of cases. Incidence of surgical site infection in each group was 17.4%, 36.8%, 32.7%, and 14.2%, respectively (p < 0.001). Multivariate analysis showed no effect of mesh selection on risk of surgical site infection. Mesh was removed in 7 patients; 5 were permanent synthetic (1.2%), 1 was absorbable synthetic (1.8%), and 1 was biologic (2.6%). In 4 patients there was mesh-specific complication and the remaining meshes were removed during exploration for indications unrelated to the mesh. At a median follow-up of 30.2 months, recurrence occurred in 15.2% of patients and was significantly lower with permanent synthetic mesh. CONCLUSIONS: Permanent synthetic mesh placed in an extraperitoneal position is not only safe for VHR in a contaminated field, but it confers a significantly lower rate of surgical site infection and recurrence compared with biologic or bioabsorbable meshes.

Effect of reorientation statistics on torque response of self-propelled particles.

We consider the dynamics of self-propelled particles subject to external torques. Two models for the reorientation of self-propulsion are considered: run-and-tumble particles and active Brownian particles. Using the standard tools of nonequilibrium statistical mechanics we show that the run and tumble particles have a more robust response to torques. This macroscopic signature of the underlying reorientation statistics can be used to differentiate between the two types of self-propelled particles.