Biochemical and Morphological Abnormalities of Subchondral Bone and Their Association with Cartilage Degeneration in Spontaneous Osteoarthritis

Ren, Pengling; Huang, Niu; Cen, Haipeng; Jia, Shaowei; Gong, He; Fan, Yubo

doi:10.1007/s00223-021-00834-3

Cited by 10 publications

(9 citation statements)

References 45 publications

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“…In support of this, Wang et al 39 demonstrated progressive subchondral bone plate changes, including increased thickening, increased bone mineral, and decreased porosity in DHGPs as early as 2 months of age. This was confirmed more recently by Ren et al 24 Thus, because this study was initiated in 3-month-old DHGPs, it is likely that subchondral bone changes had already been initiated. Furthermore, it has been noted that these bony changes preceded microscopic cartilage degeneration.…”

Section: Discussionsupporting

confidence: 80%

Human Adipose- and Amnion-Derived Mesenchymal Stromal Cells Similarly Mitigate Osteoarthritis Progression in the Dunkin Hartley Guinea Pig

et al. 2022

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Background: Clinical trials are currently underway to investigate the efficacy of intra-articular administration of mesenchymal stromal cells (MSCs) to mitigate osteoarthritis (OA) progression in the knee. Although multiple MSC sources exist, studies have yet to determine whether differences in therapeutic efficacy exist between them. Purpose: To compare the ability of intra-articularly injected adipose-derived MSCs (AD-MSCs) and amnion-derived MSCs (AM-MSCs) to mitigate the progression of knee OA in a small animal model of spontaneous OA, as well as to compare the therapeutic potential of MSCs in hyaluronic acid (HA) and in HA only with saline (OA) controls. Study Design: Controlled laboratory study. Methods: Injections of AD-MSCs or AM-MSCs suspended in HA or HA only were performed in the rear stifle joints of 3-month-old Dunkin Hartley guinea pigs (DHGPs). Repeat injections occurred at 2 and 4 months after the initial injection in each animal. Contralateral limbs received saline injections and served as untreated controls. Subsequently, joints were analyzed for osteoarthritic changes of the cartilage and subchondral bone via histologic and biochemical analyses. To evaluate MSC retention time in the joint space, DHGPs received a single intra-articular injection of fluorescently labeled AD-MSCs or AM-MSCs, and the fluorescence intensity was longitudinally tracked via an in vivo imaging system. Results: No statistically significant differences in outcomes were found when comparing the ability of AD-MSCs and AM-MSCs to mitigate OA. However, the injection of AD-MSCs, AM-MSCs, and HA-only treatments more effectively mitigated cartilage damage compared with that of saline controls by demonstrating higher amounts of cartilage glycosaminoglycan content and improved histological proteoglycan scoring while reducing the percentage of osteophytes present. Conclusion: Intra-articular injection of AD-MSCs, AM-MSCs, or HA only was able to similarly mitigate the progression of cartilage damage and reduce the percentage of osteophytes compared with that of saline controls in the DHGP. However, this study was unable to establish the superiority of AD-MSCs versus AM-MSCs as a treatment to mitigate spontaneous OA. Clinical Relevance: MSCs demonstrate the ability to mitigate the progression of knee OA and thus may be used in a prophylactic approach to delay the need for end-stage treatment strategies.

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Section: Discussionsupporting

confidence: 80%

Human Adipose- and Amnion-Derived Mesenchymal Stromal Cells Similarly Mitigate Osteoarthritis Progression in the Dunkin Hartley Guinea Pig

et al. 2022

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“…Porosity of the subchondral bone plate mirrors cavities, invading vascularized channels and extensions of the marrow space ( 30 ). The decreased closed, open, and total porosity in neutral OA, together with its increased thickness, may reflect a reinforced structural barrier secondary to the focal meniscal and cartilage loss, also observed in guinea pigs ( 6 ) and rabbits ( 7 ), possibly promoting degeneration ( 31 ). Vascular canal density in the subchondral bone plate first increases then decreases in human OA, whereas its hydraulic conductance progressively advances over the course of the disease ( 8 ), supporting the functional and dynamic role of subchondral bone plate porosity in the cross-talk between the subchondral bone and the articular cartilage during OA ( 9 ).…”

Section: Discussionmentioning

confidence: 97%

“…In the course of the disease, the subchondral bone is progressively remodeled (1). The subchondral bone plate becomes thicker and stiffer, the subarticular trabecular bone volume and its complexity decrease, and osteophytes develop (1,(3)(4)(5)(6)(7)(8)(9). These changes alter local shear stresses, which increase cartilage deformation and predispose it to splitting, whereas pathological cross-talk within the cells of the osteochondral unit further contributes to OA development (1).…”

Section: Introductionmentioning

confidence: 99%

Axial alignment is a critical regulator of knee osteoarthritis

et al. 2022

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Although osteoarthritis (OA), a leading cause of disability, has been associated with joint malalignment, scientific translational evidence for this link is lacking. In a clinical case study, we provide evidence of osteochondral recovery upon unloading symptomatic isolated medial tibiofemoral knee OA associated with varus malalignment. By mapping response correlations at high resolution, we identify spatially complex degenerative changes in cartilage after overloading in a clinically relevant ovine model. We further report that unloading diminishes OA cartilage degeneration and alterations of critical parameters of the subchondral bone plate in a similar topographic fashion. Last, therapeutic unloading shifted the articular cartilage and subchondral bone phenotype to normal and restored several physiological correlations disturbed in neutral and varus OA, suggesting a protective effect on the integrity of the entire osteochondral unit. Collectively, these findings identify modifiable trajectories with considerable translational potential to reduce the burden of human OA.

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“…At 5 months, we observed severe PG loss, at 6 months increased fibrillation, and at 9 months accentuated hypocellularity, with chondrocyte clustering, tidemark duplication, and fissures. At 12 months, the surface was eroded until complete cartilage loss at 15 months [16][17][18][19]. OARSI and Mankin scores worsened with aging, as well as CT, instantaneous modulus, cellularity, matrix integrity, insulin growth factor 1 (IGF1), and receptor activator of nuclear factor kappa-B ligand (RANKL) [20][21][22][23].…”

Section: Naturally Occurring Oa In Guinea Pigsmentioning

confidence: 99%

“…OARSI and Mankin scores worsened with aging, as well as CT, instantaneous modulus, cellularity, matrix integrity, insulin growth factor 1 (IGF1), and receptor activator of nuclear factor kappa-B ligand (RANKL) [20][21][22][23]. During aging, as regards SB, an increase in Tb.Th and osteoprotegerin (OPG) and a decrease in bone volume/tissue volume (BV/TV), trabecular bone pattern factor (Tb.Pf), and structure model index (SMI) were observed [17,18,20]. The trabecular bone area decreased in severe OA compared to mild OA with no intraosseous thrombi [16,24].…”

Section: Naturally Occurring Oa In Guinea Pigsmentioning

confidence: 99%

Naturally Occurring Osteoarthritis Features and Treatments: Systematic Review on the Aged Guinea Pig Model

Veronesi

Salamanna

Martini

et al. 2022

IJMS

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To date, several in vivo models have been used to reproduce the onset and monitor the progression of osteoarthritis (OA), and guinea pigs represent a standard model for studying naturally occurring, age-related OA. This systematic review aims to characterize the guinea pig for its employment in in vivo, naturally occurring OA studies and for the evaluation of specific disease-modifying agents. The search was performed in PubMed, Scopus, and Web of Knowledge in the last 10 years. Of the 233 records screened, 49 studies were included. Results showed that within a relatively short period of time, this model develops specific OA aspects, including cartilage degeneration, marginal osteophytes formation, and subchondral bone alterations. Disease severity increases with age, beginning at 3 months with mild OA and reaching moderate–severe OA at 18 months. Among the different strains, Dunkin Hartley develops OA at a relatively early age. Thus, disease-modifying agents have mainly been evaluated for this strain. As summarized herein, spontaneous development of OA in guinea pigs represents an excellent model for studying disease pathogenesis and for evaluating therapeutic interventions. In an ongoing effort at standardization, a detailed characterization of specific OA models is necessary, even considering the main purpose of these models, i.e., translatability to human OA.

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Biochemical and Morphological Abnormalities of Subchondral Bone and Their Association with Cartilage Degeneration in Spontaneous Osteoarthritis

Cited by 10 publications

References 45 publications

Human Adipose- and Amnion-Derived Mesenchymal Stromal Cells Similarly Mitigate Osteoarthritis Progression in the Dunkin Hartley Guinea Pig

Human Adipose- and Amnion-Derived Mesenchymal Stromal Cells Similarly Mitigate Osteoarthritis Progression in the Dunkin Hartley Guinea Pig

Axial alignment is a critical regulator of knee osteoarthritis

Naturally Occurring Osteoarthritis Features and Treatments: Systematic Review on the Aged Guinea Pig Model

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