Osteoarthritis from evolutionary and mechanistic perspectives

Abstract

Developmental osteogenesis and the pathologies associated with tissues that normally are mineralized are active areas of research. All of the basic cell types of skeletal tissue evolved in early aquatic vertebrates. Their characteristics, transcription factors, and signaling pathways have been conserved, even as they adapted to the challenge imposed by gravity in the transition to terrestrial existence. The response to excess mechanical stress (among other factors) can be expressed in the pathologic phenotype described as osteoarthritis (OA). OA is mediated by epigenetic modification of the same conserved developmental gene networks, rather than by gene mutations or new chemical signaling pathways. Thus, these responses have their evolutionary roots in morphogenesis. Epigenetic channeling and heterochrony, orchestrated primarily by micro-RNAs, maintain the sequence of these responses, while allowing variation in their timing that depends at least partly on the life history of the individual.

The nature of coxofemoral joint pathology across family Canidae

“…Overwhelmingly, bilateral trait presence (Table 2) likely reflected genetically programmed osteochondral unit responses to developmental stimuli or life insults from various causes (Tangredi & Lawler, 2019).…”

“…Recently, Tangredi and Lawler (2019) re‐visited the idea of stress and the osteochondral unit, as it was described by Williams et al (2013). That is, the osteochondral unit includes discrete but interacting niches: (a) chondrogenic (cartilage and its extracellular matrix); (b) osteogenic (subchondral bone, underlying trabecular bone); and (c) synovial (synovial membrane and synovial fluid) (Williams et al, 2013).…”

“…That is, the osteochondral unit includes discrete but interacting niches: (a) chondrogenic (cartilage and its extracellular matrix); (b) osteogenic (subchondral bone, underlying trabecular bone); and (c) synovial (synovial membrane and synovial fluid) (Williams et al, 2013). Multiple developmental, homeostatic, and stress‐response functions exist within each niche, with the niches intercommunicating through a number of broadly and deeply conserved signaling pathways (Tangredi & Lawler, 2019; Williams et al, 2013).…”

“…More specifically, several critical physiological signaling pathways are held in common among: (a) early growth‐development and (b) initiation and progression of OA (Tangredi & Lawler, 2019). These key pathways include bone morphogenetic proteins (BMPs) (Chen et al, 2004; Van der Kraan et al, 2010); wingless‐type mouse mammary integration rate (Wnt) (Lewiecki, 2014; Monteagudo & Lories, 2017); sry‐related high‐mobility group box 9 (SOX‐9) (Jo et al, 2014; Zhang et al, 2019); fibroblast growth factor 2 (FGF‐2) (Kavanaugh et al, 2006); and effects of reactive oxygen species (ROS) (Jaksik et al, 2014; Nunomura et al, 2012; Wang et al, 2015).…”

Osteophytes: The product of convergent evolution

“…Tangredi and Lawler (2019, p. 1) hypothesized that the osteophytes of osteoarthritis are “the response to excess mechanical stress (among other factors).” Those stresses are compressive, rather than traction in nature. Junker et al (2015) proposed a histological classification of osteophytes, based on their maturation from initial mesenchymal connective tissue.…”