Expression profile of matrix metalloproteinase-2 and -9 and their endogenous tissue inhibitors in osteonecrotic femoral heads

Abstract

Abstract. The pathogenetic mechanisms of osteonecrosis of the femoral head are unresolved to date. This study analyzed the matrix metalloprotease (MMP) and tissue inhibitor of matrix metalloprotease (TIMP) expression and activity which might add to the impaired bone matrix repair capacity affecting the balance between bone resorption and de novo bone formation in osteonecrosis of the femoral head (ONFH). Cancellous bone biopsies were taken at the femoral head and neck of patients with advanced ONFH and patients with primary osteoarthritis (OA) who were undergoing total hip arthroplasty. We assessed the gene expression levels of MMP-2 and -9, TIMP-1 and -2, IL-1ß, IL-6 and TNF-· in both biopsies. These data were corroborated by MMP activity screening, collagen profiling and ELISAs for determination of MMP, TIMP, IL-1ß, IL-6 and TNF-· concentrations. Gene expression rates of MMP-2 and TIMP-1 were higher in ONFH biopsies whereas TIMP-2 and MMP-9 gene expression was not significantly altered. MMP protein profile shifted towards increased biosynthesis of both, active and pro-MMP-2 in ONFH bone lysates and decreased pro-MMP-9 production. Expression profiles of pro-inflammatory cytokines and collagens in OA and ONFH bone lysates were highly similar. Increased biosynthesis and activation of MMP-2 in ONFH samples may add to shifting the bone matrix turnover balance towards resorption of bone macromolecules thereby counteracting new bone matrix production. OA-and ONFH-affected bone exhibits a similar pro-inflammatory cytokine and collagen expression profile suggesting a relationship on the molecular level of inflammation and collagenous matrix composition between both diseases.

Correlation between interleukin-6 expression in articular cartilage bone and osteoarthritis

“…In OA, IL-6 can stimulate chondrocytes and synovial cells to produce prostaglandin, collagenase, and metalloproteinase, which induces cartilage degradation. IL-6 can be secreted by chondrocytes in both normal individuals and OA patients, and plays an important role in the proliferation and metabolism of cartilage (Grassel et al, 2010). This study showed an elevated expression of IL-6 in the bones of OA patients, possibly due to the reason that IL-6 secretion from monocytes was facilitated by inflammatory factors including IL-1β and prostaglandin E as a consequence of the inflammatory response in the synovial tissues in OA; this suggests that elevated IL-6 and synovial inflammation are probably caused by damage of articular cartilage, which normally functions as a major secretion site for IL-6 (Lipari and Gerbino, 2013).…”

A single-nucleotide polymorphism inMMP9is associated with decreased risk of steroid-induced osteonecrosis of the femoral head

“…In addition, gelatinase A (MMP- 2) and B (MMP-9) play crucial roles in bone remodeling [7]. Both gelatinase A (MMP-2) and gelatinase B (MMP-9) are produced by osteoblasts, and MMP-9 can also be synthesized by osteoclasts [8]. MMP-2 expression is upregulated in osteoarthritic cartilage [9], and MMP-9, which regulates growth plate angiogenesis and apoptosis of hypertrophic chondrocytes, may be essential for normal bone remodeling [10].…”

“…Both MMP-2 and MMP- 9 expression are increased in the joints of rheumatoid arthritis patients [11, 12]. Additionally, MMP-2 mRNA and protein levels are up-regulated in ONFH subjects, while MMP-9 protein is overproduced in osteoarthritic bone tissue [8]. Inactivating mutations in the MMP2 gene result in bone and joint features of multicentric osteolysis with arthritis [13], and osteoclast MMP-9 expression increases in response to adrenocorticotropic hormone (ACTH) in murine models, confirming the effects of ACTH on early osteoclast differentiation [14].…”

Single-nucleotide polymorphisms of MMP2 in MMP/TIMP pathways associated with the risk of alcohol-induced osteonecrosis of the femoral head in Chinese males

“…[36] According to Keiichi Inoue, it plays a crucial role in forming and maintaining the osteocyte canalicular network, whose formation is a determining factor of bone remodeling and mineralization. [37,38] A report suggested that the abnormal expression of MMP2 causes osteolysis. [39] The upregulation of MMP2 induces the MMP/TIMP pathway, which in turn activates osteoclast bone resorption and accelerates osteoblast apoptosis and bone matrix degradation.…”