Abstract
IntroductionOestrogen depletion may influence onset and/or progression of osteoarthritis. We investigated in an ovariectomized mouse model the impact of oestrogen loss and oestrogen supplementation on articular cartilage and subchondral bone in tibia and patella, and assessed bone changes in osteoarthritis development.MethodsC3H/HeJ mice were divided into four groups: sham-operated, oestrogen depletion by ovariectomy (OVX), OVX with estradiol supplementation (OVX+E) and OVX with bisphosphonate (OVX+BP). Each mouse had one knee injected with low-dose iodoacetate (IA), and the contralateral knee was injected with saline. Cartilage was analysed histologically 12 weeks postsurgery; bone changes were monitored over time using in vivo micro-computed tomography.ResultsIn tibiae, OVX alone failed to induce cartilage damage, but OVX and IA combination significantly induced cartilage damage. In patellae, OVX alone induced significant cartilage damage, which was enhanced by IA. In both tibiae and patellae, OVX in combination with IA significantly decreased subchondral cortical thickness in an additive manner. OVX+E and OVX+BP inhibited tibial and patellar subchondral cortical thinning, inhibited patellar and tended to diminish tibial cartilage damage. In patellae, IA interacted with BP, leading to increased subchondral cortical and trabecular bone.ConclusionsThis study demonstrates the significance of oestrogen for articular cartilage and subchondral bone and maintenance of healthy joints, supporting an etiological role for altered oestrogen signaling in osteoarthritis either by directly affecting cartilage or increasing susceptibility for an osteoarthritis trigger. The data strongly support the concept of involvement of subchondral bone plate in osteoarthritis.
Highlights
Oestrogen depletion may influence onset and/or progression of osteoarthritis
We hypothesize that oestrogen depletion increases the susceptibility of tissues in the joint for changes, but an additional trigger is needed to develop osteoarthritic changes. This concurs with the idea that OA is a multifactorial disease. We addressed this hypothesis by investigating bone and cartilage changes in the proximal tibia and patella of knee joints of ovariectomized mice and ovariectomized mice receiving oestrogen replacement, combined with a mild osteoarthritis trigger induced by iodoacetate, an inhibitor of glycolysis that is an accepted model for osteoarthritis [31,32,33,34]
Effect of oestrogen depletion and oestrogen replacement OVX mice weighed more than sham ovariectomy (Sham) mice at the end of the experiment (Sham: 21.9 ± 0.6 g, OVX: 25.1 ± 0.3 g; P < 0.05), but no difference was found between OVX and OVX with estradiol supplementation (OVX+E) mice (OVX+E, 25.0 ± 1.0 g)
Summary
Oestrogen depletion may influence onset and/or progression of osteoarthritis. An investigation in people with knee pain revealed that the most common radiographic pattern is combined TFJ and PFJ disease (40%), followed by isolated PFJ OA (24%) [3]. It has been suggested in the literature that oestrogen depletion plays a role in the onset or progression of OA. Men are known to have a higher prevalence of OA than women before the age of 50 [5], but after this age the prevalence is higher in women [6,7]. The prevalence increases with age in both men and women, but in women, it increases dramatically around the age of 50 [5,8,9], which coincides with menopause
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