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Role of TNF alpha and PLF in bone remodeling in a rat model of repetitive reaching and grasping
Author(s) -
Rani Shobha,
Barbe Mary F,
Barr Ann E,
Litivn Judith
Publication year - 2010
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.22208
Subject(s) - osteocalcin , forelimb , matricellular protein , tumor necrosis factor alpha , medicine , ctgf , bone remodeling , endocrinology , inflammation , proinflammatory cytokine , periostin , growth factor , anatomy , chemistry , extracellular matrix , alkaline phosphatase , receptor , biochemistry , enzyme
We have previously developed a voluntary rat model of highly repetitive reaching that provides an opportunity to study effects of non‐weight bearing muscular loads on bone and mechanisms of naturally occurring inflammation on upper limb tissues in vivo. In this study, we investigated the relationship between inflammatory cytokines and matricellular proteins (Periostin‐like‐factor, PLF, and connective tissue growth factor, CTGF) using our model. We also examined the relationship between inflammatory cytokines, PLF and bone formation processes. Rats underwent initial training for 5 weeks, and then performed a high repetition high force (HRHF) task (12 reaches/min, 60% maximum grip force, 2 h/day, 3 days/week) for 6 weeks. We then examined the effect of training or task performance with or without treatment with a rat specific TNFα antibody on inflammatory cytokines, osteocalcin (a bone formation marker), PLF, CTGF, and behavioral indicators of pain or discomfort. The HRHF task decreased grip strength and induced forepaw mechanical hypersensitivity in both trained control and 6‐week HRHF animals. Two weeks of anti‐TNFα treatment improved grip strength in both groups, but did not ameliorate forepaw hypersensitivity. Moreover, anti‐TNFα treatment attenuated task‐induced increases in inflammatory cytokines (TNFα, IL‐1α, and MIP2 in serum; TNFα in forelimb bone and muscles) and serum osteocalcin in 6‐week HRHF animals. PLF levels in forelimb bones and flexor digitorum muscles increased significantly in 6‐week HRHF animals, increases attenuated by anti‐TNFα treatment. CTGF levels were unaffected by task performance or anti‐TNFα treatment in 6‐week HRHF muscles. In primary osteoblast cultures, TNFα, MIP2 and MIP3a treatment increased PLF levels in a dose dependent manner. Also in primary osteoblast cultures, increased PLF promoted proliferation and differentiation, the latter assessed by measuring Runx2, alkaline phosphatase (ALP) and osteocalcin mRNA levels; ALP activity; as well as calcium deposition and mineralization. Increased PLF also promoted cell adhesion in MC3T3‐E1 osteoblast‐like cell cultures. Thus, tissue loading in vivo resulted in increased TNFα, which increased PLF, which then induced anabolic bone formation, the latter results confirmed in vitro. J. Cell. Physiol. 225: 152–167, 2010. © 2010 Wiley‐Liss, Inc.