
Extracellular Matrix Mediates BMP-2 in a Model of Temporomandibular Joint Osteoarthritis
Author(s) -
Maya Shirakura,
Vardit Kram,
Jennifer L. Robinson,
S.S. Sikka,
Tina M. Kilts,
Sunil Wadhwa,
Marian F. Young
Publication year - 2017
Publication title -
cells tissues organs
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.662
H-Index - 82
ISSN - 1422-6405
DOI - 10.1159/000464102
Subject(s) - biglycan , cartilage , chemistry , osteoarthritis , osteoclast , extracellular matrix , microbiology and biotechnology , medicine , endocrinology , anatomy , biology , pathology , decorin , proteoglycan , biochemistry , in vitro , alternative medicine
Temporomandibular joint (TMJ) osteoarthritis (OA) is a complex disease that affects both cartilage and subchondral bone. It is accompanied by loss of extracellular matrix (ECM) and may be controlled by bone morphogenetic protein-2 (BMP-2). We analyzed the effect of BMP-2 in both cartilage and subchondral bone in a TMJ-OA animal model that is deficient in biglycan (Bgn) and fibromodulin (Fmod) (Bgn-/-Fmod-/-). Whole mandibles were dissected from 3-week-old wild-type (WT) and Bgn-/-Fmod-/- mice and incubated with and without 250 µg/mL BMP-2 for 2 days using an explant culture system. Condyle growth was measured by microCT and the expression levels of cartilage and bone-related genes were analyzed using RT-PCR or by immunohistochemistry from condyles that contained an intact cartilage/subchondral bone interface. Osteoclast activity was estimated by tartrate-resistant acid phosphatase (TRAP) staining and by TRAP, Rankl, and Adamts4 mRNA expression levels. Our results showed that most parameters examined were slightly up-regulated in WT samples treated with BMP-2, and this up-regulation was significantly enhanced in the Bgn-/-Fmod-/- mice. The up-regulation of both catabolic and anabolic agents did not appear to positively affect the overall growth of Bgn-/-Fmod-/- condyles compared to WT controls. In summary, the up-regulation of both anabolic and catabolic genes in the WT and Bgn-/-Fmod-/- TMJs treated with BMP-2 suggests that BMP increases matrix turnover in the condyle, and, further, that Bgn and Fmod could have protective roles in regulating this process.