Synovial lining macrophages mediate osteophyte formation during experimental osteoarthritis

Blom, A.B.; Lent, P.L.E.M. van; Holthuysen, A.E.M.; Kraan, P.M. van der; Roth, Johannes; Rooijen, Nico van; Berg, Wim B. van den

doi:10.1016/j.joca.2004.03.003

Cited by 318 publications

(298 citation statements)

References 32 publications

(32 reference statements)

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“…We have previously reported the presence of mature tissue macrophages closely associated with bone (6). It is also known that macrophages can express and secrete osteoactive cytokines (35), matrix metalloproteinases (36), and bone morphogenetic proteins (35).…”

Section: Discussionmentioning

confidence: 90%

“…The intimate relationship between these two systems has been primarily demonstrated in pathological conditions. Macrophages were recognized during fracture repair (33), arteriole calcification (34), and at sites of osteophyte formation in OA animal models (35). Additionally, macrophages were found at sites of pathological bone destruction (36) and contributed to systemic mechanisms in an animal model of osteoporosis (37).…”

Section: Discussionmentioning

confidence: 99%

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Osteal Tissue Macrophages Are Intercalated throughout Human and Mouse Bone Lining Tissues and Regulate Osteoblast Function In Vitro and In Vivo

Chang

Raggatt

Alexander

et al. 2008

The Journal of Immunology

618

646

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Resident macrophages are an integral component of many tissues and are important in homeostasis and repair. This study examines the contribution of resident tissue macrophages to bone physiology. Using immunohistochemistry, we showed that a discrete population of resident macrophages, OsteoMacs, was intercalated throughout murine and human osteal tissues. OsteoMacs were distributed among other bone lining cells within both endosteum and periosteum. Furthermore, OsteoMacs were coisolated with osteoblasts in murine bone explant and calvarial preparations. OsteoMacs made up 15.9% of calvarial preparations and persisted throughout standard osteoblast differentiation cultures. Contrary to previous studies, we showed that it was OsteoMacs and not osteoblasts within these preparations that responded to pathophysiological concentrations of LPS by secreting TNF. Removal of OsteoMacs from calvarial cultures significantly decreased osteocalcin mRNA induction and osteoblast mineralization in vitro. In a Transwell coculture system of enriched osteoblasts and macrophages, we demonstrated that macrophages were required for efficient osteoblast mineralization in response to the physiological remodeling stimulus, elevated extracellular calcium. Notably, OsteoMacs were closely associated with areas of bone modeling in situ, forming a distinctive canopy structure covering >75% of mature osteoblasts on diaphyseal endosteal surfaces in young growing mice. Depletion of OsteoMacs in vivo using the macrophage-Fas-induced apoptosis (MAFIA) mouse caused complete loss of osteoblast bone-forming surface at this modeling site. Overall, we have demonstrated that OsteoMacs are an integral component of bone tissues and play a novel role in bone homeostasis through regulating osteoblast function. These observations implicate OsteoMacs, in addition to osteoclasts and osteoblasts, as principal participants in bone dynamics.

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Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Osteal Tissue Macrophages Are Intercalated throughout Human and Mouse Bone Lining Tissues and Regulate Osteoblast Function In Vitro and In Vivo

Chang

Raggatt

Alexander

et al. 2008

The Journal of Immunology

618

646

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show abstract

“…Once activated, macrophages can produce large quantities of growth factors, enzymes, and proinflammatory cytokines. It has previously been shown that macrophages enhance osteophyte growth in animal models of OA (1,2). Furthermore, it is possible that macrophages play a role in the maintenance and progression of the disease by their contribution to synovial fibrosis, cartilage catabolism, and maintenance of an inflammatory state in the joint (3,4) by production of growth factors (5,6), enzymes (7), and cytokines, respectively (8,9).…”

mentioning

confidence: 99%

Imaging of activated macrophages in experimental osteoarthritis using folate-targeted animal single-photon-emission computed tomography/computed tomography

Piscaer

Müller

Mindt

et al. 2011

Arthritis & Rheumatism

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Objective. Evaluation of macrophage activation may provide essential information about the etiology and progression rate of osteoarthritis (OA). Activated macrophages abundantly express folate receptor ␤ (FR␤), which can be targeted using radioactive-labeled folic acid. This study was undertaken to investigate whether macrophage activation can be monitored in small animal models of OA using a folate radiotracer and to determine whether macrophage activation differs in different models of OA with different OA progression.Methods. Two rat models of OA were used: the mono-iodoacetate (MIA) model, which is a fastprogressing biochemically induced model, and the anterior cruciate ligament transection (ACLT) model, which induces OA at a slower pace. Images were obtained using high-resolution small animal singlephoton-emissioncomputedtomography/computedtomography. The specificity of the technique was tested by eradicating macrophages using clodronate-laden liposomes and blockade of FR␤ by cold folic acid.Results. The MIA model had high initial macrophage activation, with a peak after 2 weeks which disappeared after 8 weeks. The ACLT model showed less activation but was still active 12 weeks after induction. The technique allowed monitoring of the disease process over time, in which late stages of the disease showed less macrophage activation than early stages, especially in the fast-progressing MIA model of OA.Conclusion. Our findings indicate that macrophage activation in experimental OA can clearly be demonstrated and monitored by the folate radiotracer. The high resolution, high sensitivity, and high specificity of the technique allow clear localization of macrophage activity in a disease model that is not known for abundant macrophage involvement.

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“…Changing weight mechanics and pressure forces as well as alterations in oxygen tension and dynamic fluid pres-sure appear to be influential factors in osteophyte formation [14]. Mesenchymal stem cells of the synovium or periostium are likely precursors, with synovial macrophages and a milieu of growth factors and extracellular matrix molecules acting as probable mediators in this process [29].…”

Section: Phase IIImentioning

confidence: 99%

Lumbar Degenerative Disc Disease: Clinical Presentation and Treatment Approaches

Gupta¹,

Attry²,

Vashisth³

et al. 2016

IOSR

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Synovial lining macrophages mediate osteophyte formation during experimental osteoarthritis

Cited by 318 publications

References 32 publications

Osteal Tissue Macrophages Are Intercalated throughout Human and Mouse Bone Lining Tissues and Regulate Osteoblast Function In Vitro and In Vivo

Osteal Tissue Macrophages Are Intercalated throughout Human and Mouse Bone Lining Tissues and Regulate Osteoblast Function In Vitro and In Vivo

Imaging of activated macrophages in experimental osteoarthritis using folate-targeted animal single-photon-emission computed tomography/computed tomography

Lumbar Degenerative Disc Disease: Clinical Presentation and Treatment Approaches

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