Division of Rheumatology, Allergy and Immunology, University of North Carolina at Chapel Hill, 3300 Thurston Bldg, Campus Box 7280, Chapel Hill, NC 27599, USA.
Program of Regenerative Medicine, Center for Applied Medical Research (CIMA), Universidad de Navarra, 31008 Pamplona, Spain.
Biomolecules. 2023 May 26;13(6):891. doi: 10.3390/biom13060891.
In osteoarthritis (OA), bone changes are radiological hallmarks and are considered important for disease progression. The C-C chemokine receptor-2 (CCR2) has been shown to play an important role in bone physiology. In this study, we investigated whether osteoblast-specific inactivation at different times during post-traumatic OA (PTOA) progression improves joint structures, bone parameters, and pain. We used a tamoxifen-inducible inactivation in Collagen1α-expressing cells to obtain osteoblasts lacking (-). We stimulated PTOA changes in - and +/+ mice using the destabilization of the meniscus model (DMM), inducing recombination before or after DMM (early- vs. late-inactivation). Joint damage was evaluated at two, four, eight, and twelve weeks post-DMM using multiple scores: articular-cartilage structure (ACS), Safranin-O, histomorphometry, osteophyte size/maturity, subchondral bone thickness and synovial hyperplasia. Spontaneous and evoked pain were assessed for up to 20 weeks. We found that early osteoblast- inactivation delayed articular cartilage damage and matrix degeneration compared to +/+, as well as DMM-induced bone thickness. Osteophyte formation and maturation were only minimally affected. Late Collagen1α- deletion led to less evident improvements. Osteoblast- deletion also improved static measures of pain, while evoked pain did not change. Our study demonstrates that expression in osteoblasts contributes to PTOA disease progression and pain by affecting both cartilage and bone tissues.
在骨关节炎（OA）中，骨骼变化是放射学的标志，被认为对疾病进展很重要。C-C 趋化因子受体-2（CCR2）在骨生理学中发挥着重要作用。在这项研究中，我们研究了在创伤后 OA（PTOA）进展的不同时间点特异性敲除成骨细胞是否能改善关节结构、骨参数和疼痛。我们使用了一种在 Col1α 表达细胞中诱导的 tamoxifen 诱导失活来获得缺乏（-）的成骨细胞。我们使用半月板不稳定模型（DMM）刺激 PTOA 变化，在 DMM 之前或之后诱导重组（早期与晚期失活）。在 DMM 后 2、4、8 和 12 周，使用多个评分评估关节损伤：关节软骨结构（ACS）、番红 O、组织形态计量学、骨赘大小/成熟度、软骨下骨厚度和滑膜增生。评估自发和诱发疼痛长达 20 周。我们发现与+/+相比，早期成骨细胞失活延迟了关节软骨损伤和基质退化，以及 DMM 诱导的骨厚度增加。骨赘形成和成熟仅受到轻微影响。晚期 Col1α 缺失导致改善不明显。成骨细胞缺失还改善了静态疼痛测量值，而诱发疼痛没有改变。我们的研究表明，成骨细胞中的表达通过影响软骨和骨骼组织，促进了 PTOA 疾病进展和疼痛。
