Macrophages—Key cells in the response to wear debris from joint replacements

Abstract

The generation of wear debris is an inevitable result of normal usage of joint replacements. Wear debris particles stimulate local and systemic biological reactions resulting in chronic inflammation, periprosthetic bone destruction, and eventually, implant loosening and revision surgery. The latter may be indicated in up to 15% patients in the decade following the arthroplasty using conventional polyethylene. Macrophages play multiple roles in both inflammation and in maintaining tissue homeostasis. As sentinels of the innate immune system, they are central to the initiation of this inflammatory cascade, characterized by the release of pro-inflammatory and proosteoclastic factors. Similar to the response to pathogens, wear particles elicit a macrophage response, based on the unique properties of the cells belonging to this lineage, including sensing, chemotaxis, phagocytosis, and adaptive stimulation. The biological processes involved are complex, redundant, both local and systemic, and highly adaptive. Cells of the monocyte/ macrophage lineage are implicated in this phenomenon, ultimately resulting in differentiation and activation of bone resorbing osteoclasts. Simultaneously, other distinct macrophage populations inhibit inflammation and protect the bone-implant interface from osteolysis. Here, the current knowledge about the physiology of monocyte/macrophage lineage cells is reviewed. In addition, the pattern and consequences of their interaction with wear debris and the recent developments in this field are presented.

Do Genetic Susceptibility, Toll-like Receptors, and Pathogen-associated Molecular Patterns Modulate the Effects of Wear?

“…Those associations with aseptic loosening, in combination with those in genes that encode for proinflammatory cytokines, confirm the well-accepted concept [35,38,75,108] that aseptic loosening is primarily driven by the following stepwise process: (1) wear particles induce production of proinflammatory cytokines; (2) the proinflammatory cytokines stimulate production of RANKL; (3) RANKL increases osteoclast differentiation; and (4) the increased number of osteoclasts causes local osteolysis.…”

“…Also consistent with the importance of other factors is the finding that monocyte production of proinflammatory cytokines in response to polyethylene and titanium wear particles varies greatly between individual donors [31,46]. The similar finding with different types of particles is not surprising because the different types of particles are thought to induce osteolysis through similar proinflammatory mechanisms [7,75,102,108]. This review focuses on three other factors that may modulate the effects of wear particles: (1) genetic susceptibility; (2) Toll-like receptors (TLRs); and (3) bacterial pathogenassociated molecular patterns (PAMPs).…”

“…Moreover, there is extensive evidence that endogenous alarmins (also known as danger-associated molecular patterns) can activate TLRs [9,69]. A number of investigators have therefore concluded that TLR activation during aseptic loosening is primarily the result of alarmins rather than PAMPs [13,40,57,75,82]. For example, one of those papers concluded that UHMWPE particles induce production by monocytes of an alarmin known as hsp70 that, in turn, activates TLR4 [40].…”

“…2B). For example, alarmins may contribute to inflammasome activation by wear particles [13,57,75]. However, the relative importance of alarmins and PAMPs remains unknown in patients with aseptic loosening.…”

Role of Mesenchymal Multipotent Stromal Cells in Remodeling of Bone Defects

“…NK-клетки с ангиогенными свойствами могут индуцироваться из периферических NK-клеток при комбинации гипоксии, TGF-β и де-метилирующих агентов [10]. Опосредованный NK-ангиогенез регулируется МСК в перифери-ческих тканях и способствует индукции репара-тивных процессов после воспаления [45]. Способность МСК контролировать тече-ние инфекции определяется множественными взаимо дополняющими механизмами, в том числе усилением антимикробной активности эффекто-ров врожденного иммунитета и стимуляцией ре-паративных процессов, что может иметь важное значение при замещении дефектов костей био-имплантатами.…”