Osteoarthritis (OA) is a pathology characterized by the destruction of the cartilage and joint dysfunction [
1,
2]. The cartilage has been always described as an avascular and hypoxic tissue. This is the reason why mitochondria did not have been extensively studied in this tissue. However, our group has previously described that the activity of the mitochondrial respiratory chain (MRC) complexes II and III is reduced in human OA chondrocytes in culture compared to healthy chondrocytes [
3,
4]. In addition, some haplogroups that codify for genes related to the MRC, confer a higher predisposition to develop the OA disease [
5]. In addition, some proinflammatory factors, like cytokines IL-1β and TNF-α, produce a decrease in the activity of the MRC complex I [
6]. Among other substances produced by the tissues in the OA joint, nitric oxide (NO) has an important role on the mitochondrial activity [
7,
8]. Our group described that the NO donor sodium nitroprusside (SNP), reduced the activity of the MRC complex IV [
9]. Other groups have related the dysfunction of the MRC complex I to the NO production [
10]. In previous studies, our group has also demonstrated that the MRC dysfunction could generate an inflammatory response in the chondrocyte with upregulation of COX-2 and PGE2 production [
11‐
13].
The progressive degradation of the extracellular matrix (ECM) in the tissues like cartilage, bone and synovial tissue is one of the most common events in the rheumatic pathologies [
14]. Despite a high number of proteases contribute to the tissue destruction, the family of metalloproteases (MMPs) plays an important role. The MMPs are endopeptidase zinc and calcium dependent enzymes, secreted by resident cells in the tissues as well as by invading cells. Their function is to remodel the ECM in physiological processes (embryogenesis, cellular migration, angiogenesis) and in pathological processes like (tumours, rheumatic pathologies, cardiovascular diseases) [
15]. Collagenase 1 or MMP-1, was the first MMP that was described. It is widely expressed in connective tissues like fibroblasts, chondrocytes, monocytes, macrophages and oncogenic cells. It breaks collagen III but also collagen I, II, VII, VIII, X and gelatine. It activates the pro MMP-2 and -9. MMP-13 or collagenase-3 degrades collagen II and collagen I, III, IV, IX, X, XIV, gelatine, laminin, aggrecane and fibronectin [
16]. Stromelisin 1 or MMP-3 is expressed in fibroblasts, osteoblasts, osteblasts and chondrocytes. Its targets are collagen II, IV, IX, X, XI and gelatine, as well as elastine, caseine, laminin, fibrinogen and aggrecan. It also activates other procollagenases (-1, -8, -13) and pro MMP-9 [
17]. It is highly expressed in late OA phases. There is a direct relation between MMP-3 levels and the OA severity grade [
18,
19]. Some studies have demonstrated how hyaluronic acid reduces the MMP-3 expression and the cartilage destruction [
20‐
22]. Considering the importance of MMPs in the integrity of the cartilage, and given the role of the mitochondria in the chondrocyte physiology, we evaluated the modulation of MMPs after mitochondrial dysfunction.