PMID- 30550849
OWN - NLM
STAT- MEDLINE
DCOM- 20200219
LR  - 20200219
IS  - 1873-2763 (Electronic)
IS  - 1873-2763 (Linking)
VI  - 120
DP  - 2019 Mar
TI  - Osteocytes reflect a pro-inflammatory state following spinal cord injury in a 
      rodent model.
PG  - 465-475
LID - S8756-3282(18)30449-6 [pii]
LID - 10.1016/j.bone.2018.12.007 [doi]
AB  - Profound bone loss occurs following spinal cord injury (SCI) resulting in a high 
      incidence of fractures. While likely caused in part by loss of weight-bearing, 
      there is greater bone loss following SCI when compared to that observed in other 
      disuse animal models. Patients with SCI have a protracted inflammatory response, 
      with elevated circulating levels of pro-inflammatory markers. This chronic 
      inflammation could compound the bone loss attributed to disuse and the loss of 
      neural signaling. To assess this, we examined inflammatory markers and bone 
      turnover regulators in osteocytes from rats with a moderate spinal contusion 
      injury (SCI) and intact controls (CON). We counted osteocytes positive for 
      cytokines [tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and 
      interleukin-17 (IL-17), and interleukin-10 (IL-10)], osteoclastogenesis 
      regulators RANKL and OPG, and the bone formation inhibitor sclerostin, 32 days 
      after the spinal contusion. By day 9 post-injury, the majority of SCI rats had 
      recovered significant locomotor function and were bearing weight on their 
      hindlimbs. However, despite weight-bearing, peripheral QCT scans demonstrated 
      lower bone mass due to SCI in the proximal tibia metaphysis compared to CON. SCI 
      animals also had lower cancellous bone volume, lower bone formation rate (BFR), 
      lower osteoid surface (OS), and higher osteoclast surface (Oc.S). Tibial 
      mid-shaft periosteal BFR was also lower after SCI. Immunohistochemical staining 
      of the distal femur bone revealed cancellous osteocytes positive for TNF-alpha, IL-6, 
      IL-17, and IL-10 were elevated in SCI animals relative to intact controls. 
      Protein expression of RANKL+, OPG+, and sclerostin+ osteocytes was also higher in 
      SCI rats. At the cortical midshaft, osteocyte TNF-alpha, IL-6, and sclerostin were 
      statistically higher in SCI vs. CON. With regression analysis, inflammatory 
      factors were associated with changes in bone turnover. In conclusion, 
      inflammatory factors as well as altered mechanical loading influence bone 
      turnover following a moderate SCI. Treatments aimed at minimizing fracture risk 
      after SCI may need to target both the chronically altered inflammatory state as 
      well as disuse-induced bone loss.
CI  - Copyright (c) 2018 Elsevier Inc. All rights reserved.
FAU - Metzger, Corinne E
AU  - Metzger CE
AD  - Department of Health and Kinesiology, Texas A&M University, College Station, TX, 
      United States of America. Electronic address: metzgercorinne@gmail.com.
FAU - Gong, Sammy
AU  - Gong S
AD  - Department of Neuroscience and Experimental Therapeutics, Texas A&M Health 
      Science Center, Bryan, TX, United States of America.
FAU - Aceves, Miriam
AU  - Aceves M
AD  - Department of Neuroscience and Experimental Therapeutics, Texas A&M Health 
      Science Center, Bryan, TX, United States of America.
FAU - Bloomfield, Susan A
AU  - Bloomfield SA
AD  - Department of Health and Kinesiology, Texas A&M University, College Station, TX, 
      United States of America.
FAU - Hook, Michelle A
AU  - Hook MA
AD  - Department of Neuroscience and Experimental Therapeutics, Texas A&M Health 
      Science Center, Bryan, TX, United States of America. Electronic address: 
      hook@medicine.tamhsc.edu.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20181211
PL  - United States
TA  - Bone
JT  - Bone
JID - 8504048
RN  - 0 (Bone Morphogenetic Proteins)
RN  - 0 (Genetic Markers)
RN  - 0 (Sost protein, rat)
SB  - IM
MH  - Animals
MH  - Bone Morphogenetic Proteins/metabolism
MH  - Cortical Bone/pathology/physiopathology
MH  - Disease Models, Animal
MH  - Femur/pathology/physiopathology
MH  - Genetic Markers
MH  - Hindlimb/physiopathology
MH  - Inflammation/complications/*pathology
MH  - Linear Models
MH  - Male
MH  - Organ Size
MH  - Osteocytes/metabolism/*pathology
MH  - Osteogenesis
MH  - Periosteum/pathology/physiopathology
MH  - Rats, Sprague-Dawley
MH  - Spinal Cord Injuries/complications/diagnostic imaging/*pathology
MH  - Tibia/pathology/physiopathology
MH  - Weight-Bearing
OTO - NOTNLM
OT  - Cytokines
OT  - Inflammation
OT  - Osteocytes
OT  - Spinal cord injury
EDAT- 2018/12/15 06:00
MHDA- 2020/02/20 06:00
CRDT- 2018/12/15 06:00
PHST- 2018/08/17 00:00 [received]
PHST- 2018/12/06 00:00 [revised]
PHST- 2018/12/10 00:00 [accepted]
PHST- 2018/12/15 06:00 [pubmed]
PHST- 2020/02/20 06:00 [medline]
PHST- 2018/12/15 06:00 [entrez]
AID - S8756-3282(18)30449-6 [pii]
AID - 10.1016/j.bone.2018.12.007 [doi]
PST - ppublish
SO  - Bone. 2019 Mar;120:465-475. doi: 10.1016/j.bone.2018.12.007. Epub 2018 Dec 11.